Browsing by Subject "Adenocarcinoma"
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- PublicationOpen AccessAcetyl-and butyrylcholinesterase activities decrease in human colon adenocarcinoma(Springer, 2006-02) Montenegro Arce, María Fernanda; Ruiz Espejo, Francisco; Campoy Menéndez, Francisco Javier; Muñoz Delgado, Encarnación; Páez de la Cadena, María; Cabezas Herrera, Juan; Vidal, Cecilio J.; Bioquímica y Biología Molecular AApart from the hydrolysis of acetylcholine (ACh), acetyl- (AChE) and butyrylcholinesterase (BChE), through noncatalytic mechanisms, intervene in hematopoiesis, morphogenesis, and neurogenesis (Layer and Willbold, 1995; Soreq and Seidman, 2001). Cholinesterase (ChE) molecules occur as globular (G1, G2, and G4) and asymmetric (A4, A8, and A12) forms (Legay, 2000; Massoulié, 2002). The G species might display amphiphilic (GA) or hydrophilic (GH) properties (Perrier et al., 2002). The involvement of ChEs in tumorigenesis is supported by the measurement of ChE activity in tumors (García-Ayllón et al., 2001; Ruiz-Espejo et al., 2003), the amplification of ChE genes in leukemias and ovarian tumors, and the relationship between the expression of AChE and the aggressiveness of astrocytomas(Perry et al., 2002). This research was undertaken to determine whether ChE activity is altered in gut carcinomas.
- PublicationOpen AccessAdenocarcinoma of the paraurethral glands: a case report(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Massari, Francesco; Ciccarese, Chiara; Modena, Alessandra; Maines, Francesca; Segala, Diego; Luchini, Claudio; Marcolini, Lisa; Cavicchioli, Francesca; Cavalleri, Stefano; Bria, Emilio; Brunelli, Matteo; Martignoni, Guido; Artibani, Walter; Tortora, GiampaoloAdenocarcinoma of the paraurethral glands represents a very rare neoplasm of the urinary tract. Due to the rarity of this disease, there is no standard therapeutic approach. We report a case of adenocarcinoma of the paraurethral glands in a 56-year-old woman, presenting with abnormal serous vaginal discharges. The radiologic examination revealed a 5-cm mass around the urethra, which underwent surgical resection. After surgical resection, the histology revealed a moderately differentiated adenocarcinoma, probably arising from the paraurethral glands. One month later, a pelvic recurrent mass was radiologically diagnosed; consequently, an anterior pelvic exenteration with lymph node dissection was performed. Histological examination revealed a moderately differentiated adenocarcinoma, with glandular and micropapillary architecture, with multiple lymph node metastases. The absence of modifications such as urethritis cystic glandularis on the urethral mucosa, as well as the lack of a lesion in situ, associated with the immunohistochemical expression of PAX8 and negativity for GATA3 and S100p, suggested that the adenocarcinoma originated from the paraurethral glands rather than from the urethral mucosa. Post-surgery CT scans revealed no evidence of metastatic disease. The patient received 6 courses of adjuvant chemotherapy with carboplatin and paclitaxel. One year after the pelvic exenteration, because of inguinal lymph node progression, an inguinal lymphadenectomy was performed. Four months later, a TC-PET revealed a multidistrectual lymph node and a lung micronodule disease progression. Invasive micropapillary carcinomas have been characterized as a rare distinctive variant of carcinomas in several anatomic sites and are distinguished by a marked tendency to lymphovascular invasion, justifying the association with high-stage disease and poor prognosis. In the present case, both the poor prognosis connected with micropapillary structure and the lymph node involvement, encouraged adjuvant cisplatinumbased chemotherapy.
- PublicationOpen AccessBarrett esophagus and cancer: pathogenesis, carcinogenesis, and diagnostic dilemmas(Murcia : F. Hernández, 1999) Polkowski, W.; Van Lanschot, J.J.B.; Offerhaus, G.J.A.A metaplastic process, in which native squamous epithelium of the distal esophagus is replaced by columnar epithelium, is known as Barrett esophagus (BE). Over the past years, intestinal metaplasia was recognized as a marker for BE. The risk for the development of esophageal adenocarcinoma in a patients with BE is much hi"gh er when com~aredto the normal population. Duodeno-gastro-esophageal reflux is supposed to play a role in the pathogenesis of BE and rising incidence of adenocarcinoma of the esophagus. With current therapeutic options, when clinical manifestation of this cancer occurs, it is too late for cure in the majority of patients. Therefore, attention should be focused on early diagnosis, for which molecular genetic techniques might become available. Current data on genetic alterations involved in carcinogenesis of BE are discussed. Grading of dysplasia in BE carries important clinical consequences for the individual patient: intensification of endoscopic surveillance or 'prophylactic esophagectomy'. Several morpho- andlor cytometric parameters may be used for discrimination between different grades of dysplasia in BE. Therefore, a new and original algorythm for the potential application of quantitative pathology in grading of dysplasia in patients with BE has been proposed. Molecular biology together with image analysis of histological spectrum of BE enable better understanding of the mechanisms of malignant degeneration and might ultimately lead to targeted cancer prevention andlor therapeutic interventions.
- PublicationOpen AccessClinicopathologic and molecular characteristics of neuroendocrine carcinomas of the gallbladder(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Tang, Hui; Jiang, Xiaojun; Zhu, Lili; Xu, Liming; Wang, Xiaoxi; Li, Hong; Gao, Feifei; Liu, Xinxin; Ren, Chuanli; Zhao, YanGallbladder neuroendocrine carcinomas (GB-NECs) are a rare subtype of malignant gallbladder cancer (GBC). The genetic and molecular characteristics of GB-NECs are rarely reported. This study aims to assess the frequency of microsatellite instability (MSI) in GB-NECs and characterize their clinicopathologic and molecular features in comparison with gallbladder adenocarcinomas (GB-ADCs). Data from six patients with primary GB-NECs and 13 with GB-ADCs were collected and reevaluated. MSI assay, immunohisto-chemistry for mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2), comprehensive genomic profiling (CGP) via next-generation sequencing (NGS), and evaluation of tumor mutation burden (TMB) were conducted on these samples. The six GB-NEC cases were all female, with a mean age of 62.0±9.2 years. Of these, two cases were diagnosed as large cell neuroendocrine carcinomas (LCNECs), while the remaining four were small cell neuroendocrine carcinomas (SCNECs). Microsatellite states observed in both GB-NECs and GB-ADCs were consistently microsatellite stable (MSS). Notably, TP53 (100%, 6/6) and RB1 (100%, 6/6) exhibited the highest mutation frequency in GB-NECs, followed by SMAD4 (50%, 3/6), GNAS (50%, 3/6), and RICTOR (33%, 2/6), with RB1, GNAS, and RICTOR specifically present in GB-NECs. Immunohistochemical (IHC) assays of p53 and Rb in the six GB-NECs were highly consistent with genetic mutations detected by targeted NGS. Moreover, no statistical difference was observed in TMB between GB-NECs and GB-ADCs (p=0.864). Although overall survival in GB-NEC patients tended to be worse than in GB-ADC patients, this difference did not reach statistical significance (p=0.119). This study has identified the microsatellite states and molecular mutation features of GB-NECs, suggesting that co-mutations in TP53 and RB1 may signify a neuroendocrine inclination in GB-NECs. The IHC assay provides an effective complement to targeted NGS for determining the functional status of p53 and Rb in clinical practice.
- PublicationOpen AccessColonic endocrine cells in rats with chemically induced colon carcinoma(Murcia : F. Hernández, 2001) Sitohy, B.; El-Salhy, M.Colonic carcinoma was induced in male Sprague-Dawley rats by injecting them with 1,2- dimethylhydrazine dihydrochloride. Control rats were injected with EDTA solution. Tissue specimens of colon from four groups of animals: (i) rats without tumour, (ii) with dysplasia and lymphoid hyperplasia, (iii) with colonic adenocarcinoma, and (iv) controls, were investigated. The colonic endocrine cells were detected by immunocytochemistry and quantified by computerised image analysis. Peptide YY (PYY)- and serotonin-immunoreactive cells were found in the colon of al1 the groups investigated. There were few somatostatin- or enteroglucagon-immunoreactive cells and no pancreatic polypeptide (PP)-immunoreactive cells in the colon of any of the groups studied. The density of PYY-immunoreactive cells increased significantly in rats with dysplasia and lymphoid hyperplasia and in rats with colon carcinoma. There was no statistically significant difference as regards cell secretory index (CSI) or nuclear area of PYYimmunoreactive cells in any of treated groups examined. Nor was there any statistically significant difference between al1 treated animal groups and controls, as regards cell density, CSI, or nuclear area of serotoninimmunoreactive cells. The present observations in an animal model of human colon carcinoma support the assumption that neuroendocrine peptides in the gut are involved in the carcinogenesis of colorectal carcinoma. However, The nature of the changes in the colonic endocrine cells observed here differed from those in patients with colon carcinoma, possibly due to a difference between the response of young rats to an induced colon carcinoma and a spontaneously developed carcinoma in elderly humans, or due to a species difference.
- PublicationOpen AccessCorrelation of epithelial-mesenchymal transition markers with clinicopathologic parameters in adenocarcinomas and squamous cell carcinoma of the lung(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Kim, Seok-Hyung; Kim, Jin Man; Shin, Myeong-hee; Kim, Chul Woung; Huang, Song-Mei; Kang, Dong Wook; Suh, Kwang Sun; Yi, Eunhee S.; Kim, Kyung HeeEpithelial-mesenchymal transition (EMT) is characterized by the loss of epithelial cell junction proteins and the gain of mesenchymal markers. The aim of this study was to analyze the associations between the EMT-related markers vimentin, E-cadherin, ß-catenin, slug, snail, and twist1 and clinicopathologic parameters as well as epidermal growth factor receptor (EGFR) gene copy number and protein expression in non-small cell lung carcinoma (NSCLC). Fifty-nine squamous cell carcinomas (SCC) and 43 adenocarcinomas (AD) were immunohistochemically examined for respective EMT markers and for EGFR, using the EGFR PharmDx kit (Dako) for protein expression and automated silver enhanced in situ hybridization (SISH) for copy number. Vimentin expression in tumor epithelia was significantly higher in AD samples than in SCC samples (P=0.015). Among AD samples, vimentin expression was positively correlated with histologic grade (2 vs. 3; P=0.021) and exhibited a tendency toward a positive correlation with pTNM stage (I vs. II-IV; P=0.052). EGFR gene copy number was positively correlated with EGFR protein expression among both AD samples (P=0.008) and SCC samples (P=0.042), with EGFR protein expression being significantly higher in SCC samples compared with AD (P=0.038). Among AD samples, EGFR protein expression was associated with higher cytoplasmic expression of ß-catenin (P=0.031). Among SCC samples, EGFR protein expression was negatively correlated with nuclear expression of ß-catenin (P=0.033) but positively with nuclear slug (P=0.021). The expression pattern of EMT markers in AD suggests that vimentin is a possible immunohistochemical predictor of tumor progression
- PublicationOpen AccessDensity of CD8-positive tumor-infiltrating T-lymphocytes is an independent prognostic factor in adenocarcinoma of the esophagogastric junction(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Knief, Juliana; Lazar Karsten, Pamela; Wellner, Ulrich; Humme, Richard; Thorns, ChristophTumor-infiltrating lymphocytes (TILs) have commonly been associated with markedly improved prognosis in a variety of human cancers, including carcinomas of the upper and lower gastrointestinal tract. Especially the presence of T-cells (cytotoxic as well as helper cells) seems to define a subgroup of patients with prolonged overall and event-free survival. The density of TILs was assessed via immunohistochemistry for CD8 and CD103 in a population of 228 adenocarcinomas of the esophagogastric junction. Density of CD8+ Tlymphocytes was inversely correlated with depth of tumor infiltration (p=0.013) while no correlation with any of the analyzed clinicopathologic factors could be established for CD103-density. High density of CD8- positive T-cells additionally showed significantly longer overall survival (OS) with a p-value of 0.024 while density of CD103+ cells was associated with prolonged tumor free survival (p-value 0.011). Independence could be demonstrated applying Cox proportional hazard analysis (Hazard Ratio 0.742; 95%-Confidence Interval 0.579-0.951; p=0.019). High density of CD8-positive Tlymphocytes identifies a patient subgroup with significantly prolonged overall survival, is correlated with tumor stage and might open up new therapeutic possibilities via immunomodulating drugs.
- PublicationOpen AccessExpression of hexokinases and glucose transporters in treated and untreated oesophageal adenocarcinoma(Murcia : F. Hernández, 2009) Fonteyne, Philippe; Casneu, Veerle; Pauwels, Patrick; Van Damme, Nancy; Peeters, Marc; Dierckx, Rudi; Van de Wiele, ChristopheThe aim of this study was to assess the expression pattern of the high glucose affinity glucose transporters GLUT 1, 2, 3, 4, 8 and 9 and of hexokinases I, II and III in newly diagnosed oesophageal adenocarcinoma by means of immunohistochemistry. Twenty patients eligible to undergo primary surgery and 18 patients with incomplete pathological response following induction radio chemotherapy, all suffering from oesophageal adenocarcinoma, were included in the study. The intensity and amount of positive tumour cells in the immuno-reaction (histology score (Hscore)) for GLUT 1, 3, 4, 8 and 9 as well as for hexokinase I, II and III were assessed independently by two experienced observers, blinded to the clinical results. In patients that underwent primary surgery, Hscores of GLUT8 (µ 6.7; sd3.3) and GLUT1 (µ 5.5; sd: 5.3) were significantly higher than Hscores of GLUT9 (µ 2.2; sd 1.5) and GLUT3 (µ 3.2, sd: 2.5). Hscores of hexokinase I (µ : 8.3; sd: 4.3), II (µ 5.5, sd: 4.0) and III (Ì 1.5, sd: 0.7) were all significantly different from each other (p<0.04). In patients that underwent radiochemotherapy prior to surgical tumour resection, µ Hscores were 6.9 (sd: 4.4) for GLUT1, 6.8 (sd: 5.3) for GLUT3, 5.9 (sd: 4.2) for GLUT8, 3.4 for GLUT9 (sd: 2.7) and 2.3 (sd: 3.6) for GLUT 4. Hscores of GLUT1 and GLUT3 were significantly higher than Hscores of GLUT4. Finally, Hscores of patients with radiochemotherapy for GLUT3, hexokinase II and III were significantly higher when compared to patients that underwent primary surgery.
- PublicationOpen AccessIdentification of S100A8 and S100A9 as negative regulators for lymph node metastasis of gastric adenocarcinoma(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Choi, Jin Hwa; Shin, Na Ri; Moon, Hyun Jung; Kwon, Chae Hwa; Kim, Gwang Ha; Song, Geun Am; Jeon, Tae Yong; Kim, Dae Hwan; Kim, Dong Hun; Park, Do YounWith increasing therapeutic use of minimally invasive therapy for treatment of early gastric cancer, prediction of lymph node metastasis is important. In search of tissue biomarkers for prediction of lymph node metastasis of gastric adenocarcinoma, we analyzed gastric adenocarcinoma tissue using proteomic methods. We have done 2D-PAGE and MALDI-TOF MS analysis in matched normal and gastric cancer tissues. We also evaluated the clinicopathological significance of expression of S100A8 and S100A9 in gastric adenocarcinoma using a tissue microarray of 218 gastric adenocarcinoma specimens. Cell invasion and migration assay were performed to confirm functional role of S100A8 and S100A9 using small hairpin RNA lentivirus. We identified 8 up-regulated and 5 down-regulated proteins in gastric cancer tissues compared to matched normal mucosa. Of these, expression of S100A8 and S100A9 occurred mainly in stromal cells and inflammatory cells between tumor cells. Correlation was observed between small lesion size, decreased depth of invasion, a tendency to absence of lymphovascular tumor emboli, a decrease in perineural invasion and lymph node metastasis, and expression of stromal S100A8. In addition, increased expression of stromal S100A9 in gastric adenocarcinoma was associated with small lesion size and a decrease in lymph node metastasis. Functional analysis confirmed that down-regulation of S100A8 and S100A9 by small hairpin RNA lentivirus induced an increase of migration and invasion in gastric cancer cell lines. Taken together, these findings suggest that S100A8 and S100A9 are negative regulators of lymph node metastasis of gastric adenocarcinoma and can be used as biomarkers for prediction of lymph node metastasis in gastric adenocarcinoma.
- PublicationOpen AccessModified gleason grading. An updated review(Murcia : F. Hernández, 2009) Helpap, Burkhard; Egevad, LarsAt an ISUP (International Society of Urological Pathology) consensus conference in 2005 in San Antonio, Texas, the old Gleason grading system for prostatic carcinoma from 1966 underwent its first major revision. With this modified Grading system a shift of the most frequent Gleason scores from 6 to 7a (3+4) in biopsy specimens and an increased degree of agreement between specimens of biopsies and radical prostatectomies with carcinoma of the prostate could be demonstrated. After modified grading of GS 3+4=7a tumours 95% were stage pT2, while 79% of GS 4+3=7b tumours were stage pT3-4. In cases with PSA <10ng/ml and tumour extent <20% the most frequent Gleason scores were 6 and 7a. Cases with serum PSA >10ng/ml or tumour extent >20% had higher scores (7b or higher). Cancers with tumour infiltration of <1mm in one of 12 cores and PSA <10ng/ml were mainly low grade (Gleason scores 6 and 7a) and may correspond to so called insignificant carcinoma of the prostate. Conclusion: With the modified Gleason At an ISUP (International Society of Urological Pathology) consensus conference in 2005 in San Antonio, Texas, the old Gleason grading system for prostatic carcinoma from 1966 underwent its first major revision. With this modified Grading system a shift of the most frequent Gleason scores from 6 to 7a (3+4) in biopsy specimens and an increased degree of agreement between specimens of biopsies and radical prostatectomies with carcinoma of the prostate could be demonstrated. After modified grading of GS 3+4=7a tumours 95% were stage pT2, while 79% of GS 4+3=7b tumours were stage pT3-4. In cases with PSA <10ng/ml and tumour extent <20% the most frequent Gleason scores were 6 and 7a. Cases with serum PSA >10ng/ml or tumour extent >20% had higher scores (7b or higher). Cancers with tumour infiltration of <1mm in one of 12 cores and PSA <10ng/ml were mainly low grade (Gleason scores 6 and 7a) and may correspond to so called insignificant carcinoma of the prostate. Conclusion: With the modified Gleason system, grade, stage, tumour extent and serum PSA show good correlations and characterize the difference between low and high grade malignancy of prostate carcinoma.
- PublicationOpen AccessMyeloid sarcoma and adenocarcinoma of the large bowel as collision tumors: a case report(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Rocca, Bruno Jim; Ambrosio, M; Gozzetti, A.; Bocchia, M.; Leoncini, L.; Lazzi, S.Myeloid sarcoma is a rare tumor composed of myeloid cells, localized in an extramedullary site, which may be associated with a concurrent myeloid neoplasm involving the bone marrow, although such an association is not required. Most patients present with acute myeloid leukemia and their prognosis is poor. We describe the case of a 76-year old woman with an adenocarcinoma of the right colon infiltrating the subserosa synchronous with a myeloid sarcoma at the same site; one pericolic lymph node was infiltrated by both tumors. The peculiarities of this case are the clinical presentation (as an acute abdomen due to subserosa infiltration by the myeloid sarcoma), the coexistence of a myeloid sarcoma with an adenocarcinoma of the right colon, and the absence of progression to acute leukemia. Coexistence of myeloid sarcoma and adenocarcinoma in the colon is probably incidental, and so it appears likely that the two different tumours arose from different mechanisms. However, a possible common background is conceivable. Some authors have found that p53 has a pivotal role in driving the maturation of myeloid stem cells and p53 is, also, involved in colon carcinogenesis. In our case, it may be hypothesized that synchronous heterogeneous mutations occurred in different types of committed cells or in stem cells secondary to p53 loss. Since only one case report has evaluated the correlation between myeloid sarcoma and adenocarcinoma of the large bowel, further immunohistochemical and molecular studies are needed to clarify the pathogenetic relationship between them
- PublicationOpen AccessOverexpression of γ-tubulin in non-small cell lung cancer(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Maounis, Nicoletta F.; Dráberová, Eduarda; Mahera, Heleni; Chorti, María; Caracciolo, Valentina; Sulimenko, Tetyana; Riga, Dimitra; Trakas, Nikolaos; Emmanouilidou, Aphrodite; Giordano, Antonio; Dráber, Pavel; Katsetos, Christos D.We and others have previously shown that increased expression and altered compartmentalization of γ-tubulin may contribute to tumorigenesis and tumor progression (J. Cell Physiol. 2009;223:519-529; Cancer Biol. Ther. 2010;9:66-76). Here we have determined by immunohistochemistry the localization and cellular distribution of γ-tubulin in clinical tissue samples from 109 non-small cell lung cancer (NSCLC) cases. The expression and distribution of γ-tubulin protein and transcripts was also determined in the NSCLC tumor cell lines NCI-H460 (HTB-177) and NCI-H69 (HTB-119) by immunocytochemistry, quantitative immunoblotting and reverse transcription quantitative real-time PCR (RT-qPCR). Polyclonal and monoclonal anti-peptide antibodies recognizing epitopes in the C- or N-terminal domains of γ-tubulins and human gene-specific primers for γ-tubulins 1 (TUBG1) and 2 (TUBG2) were used. In non-neoplastic cells of the airway epithelium in situ, γ-tubulin exhibited predominantly apical surface and pericentriolar localizations. In contrast, markedly increased, albeit heterogeneous and variously prominent γ-tubulin immunoreactivity was detected in clinical tumor specimens and in the NCI-H460 and NCI-H69 cell lines, where tumor cells exhibited overlapping multi-punctate and diffuse patterns of localization. Co-expression of γ-tubulin and Ki-67 (MIB-1) was detected in a population of proliferating tumor cells. A statistically significant increase of γ-tubulin expression was found in Stage III compared to lesser stage tumors (p<0.001 v. Stages I/II) regardless of histological subtype or grade. By quantitative immunoblotting NCI-H460 and NCI-H69 cells expressed higher levels of γ-tubulin protein compared to small airway epithelial cells (SAEC). In both tumor cell lines increase in TUBG1 and TUBG2 transcripts was detected by RT-qPCR. Our results reveal for the first time an increased expression of γ-tubulin in lung cancer
- PublicationOpen AccessStructural and functional integrity of endocrine pancreas post administration of Karwinskia humboldtiana fruit to Wistar rats: a possible therapeutic application for cancer of exocrine origin(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Segoviano Ramirez, Juan Carlos; Esparza Rodriguez, Nallely; Carcano Diaz, Katya; Diaz Perez, Rosa Nelly; Palma Nicolas, Jose Prisco; Hernandez Bello, Romel; García Juárez, JaimeAims. Pancreatic adenocarcinoma represents a therapeutic challenge due to the high toxicity of antineoplastic treatments and secondary effects of pancreatectomy. T-514, a toxin isolated from Karwinskia humboldtiana (Kh) has shown antineoplastic activity on cell lines. In acute intoxication with Kh, we reported apoptosis on the exocrine portion of pancreas. One of the mechanisms of antineoplastic agents is the induction of apoptosis, therefore our main objective was to evidence structural and functional integrity of the islets of Langerhans after the administration of Kh fruit in Wistar rats. Methods. TUNEL assay and immunolabelling against activated caspase-3 were used to detect apoptosis. Also, immunohistochemical tests were performed to search for glucagon and insulin. Serum amylase enzyme activity was also quantified as a molecular marker of pancreatic damage. Results. Evidence of toxicity on the exocrine portion, by positivity in the TUNEL assay and activated caspase-3, was found. On the contrary, the endocrine portion remained structurally and functionally intact, without apoptosis, and presenting positivity in the identification of glucagon and insulin. Conclusions. These results demonstrated that Kh fruit induces selective toxicity on the exocrine portion and establish a precedent to evaluate T-514 as a potential treatment against pancreatic adenocarcinoma without affecting the islets of Langerhans.
- PublicationOpen AccessSystematic review and meta-analysis in anatomic pathology: the value of nuclear DNA content in predicting progression in low grade CIN, the significance of the histological subtype on prognosis in cervical carcinoma(Murcia : F. Hernández, 1999) Heatley, M.K.Meta-analysis, though increasingly popular in clinical medicine, has not found acceptance in anatomic pathology. This paper argues that, in combination with a systematic review of the literature, meta-analysis may be usefully applied to pathological research and two examples drawn from gynaecological pathology (the value of nuclear DNA quantitation in predicting progression in low grade cervical intraepithelia1 neoplasia and the difference in prognosis between squamous cell carcinoma and adenocarcinoma of the cervix) are included to illustrate the methods used and to demonstrate some of the difficulties associated with these techniques.
- PublicationOpen AccessTetranectin expression in gastric adenocarcinomas(Murcia : F. Hernández, 2002) Arvanitis, D.; Kamper, E.F.; Kopeikina, L.; Stavridou, A.; Sgantzos, M.; Kallioras, V.; Athanassiou, E.D.; Kanavaros, PanagiotisA i m s : The aim was to analyze the immunohistochemical localization of tetranectin in gastric adenocarcinomas and the adjacent tissues of the wall of the stomach. Methods and results: Forty cases of gastric adenocarcinomas were stained by the indirect immunoperoxidase method. Of the ten cases of mucinous signet ring cell carcinomas 5 showed high, 3 moderate and 2 low tetranectin expression. Of the ten cases of well-differentiated intestinal type adenocarcinomas (ITA) 4 showed moderate regional, 3 l ow regional and 3 nega t ive tetranectin expression. Of the ten cases of moderately-differentiated ITA 3 showed moderate regional, 4 low regional and 3 nega t ive tetranectin expression. Of the ten cases of poorlyd i fferentiated ITA 4 showed focal low and 6 nega t ive tetranectin expression. Overall, the mucinous signet ring carcinomas showed significantly higher tetranectin expression compared to ITA (c2=3.95, p<0.05). In contrast, no significant relationship was found between tetranectin expression and the degree of differentiation in I TA (c2=2.5, p>0.05). In all cases, the perineoplastic desmoplastic reactive stroma showed high expression of tetranectin intra- and extracellularly. The mast cells and goblet cells in the areas of intestinal metaplasia showed high tetranectin expression. C o n c l u s i o n s : This study s h ows that: a) tetranectin is produced and deposited extracellularly in the desmoplastic peritumoral stroma of i n filtrating gastric adenocarcinomas; b) tetranectin is more highly expressed by the mucinous signet ring cell carcinomas compared to ITA; and c) the amount of tetranectin produced by the ITA is unrelated with the degree of tumor differentiation.
- PublicationOpen AccessTumor-associated neoexpression of the pS2 peptide and MUC5AC mucin in primary adenocarcinomas and signet ring cell carcinomas of the urinary bladder(Murcia : F. Hernández, 2008) Kunze, E.; Krassenkova, I.; Fayyazi, A.To gain more detailed insight into the histogenesis of primary nonurachal adenocarcinomas and signet ring cell carcinomas of the urinary bladder, we analyzed by immunohistochemistry the expression of a broad panel of proteins, associated with cell differentiation (pS2 peptide, MUC5AC, MUC6, spasmolytic polypeptide, cyclooxygenases-1 and -2, caveolin-1), and of various novel known or candidate tumor suppressors (14-3-3 sigma, SYK, PTEN, maspin). Included were 12 adenocarcinomas admixed to urothelial carcinomas, 10 pure adenocarcinomas and 5 signet ring cell carcinomas. As the most important finding, the majority of signet ring cell carcinomas and three quarters of the adenocarcinomas (72.7%) expressed the pS2 peptide, and nearly half of the adenocarcinomas (45.5%) as well as most of the signet ring cell carcinomas were observed to secrete the MUC5AC apomucin. Since expression of both proteins was absent in the normal nonneoplastic urothelium, their tumor-associated appearance is regarded as a neoexpression or reexpression, respectively, of normally cryptic antigenic determinants, and is assumed to be involved in the phenotypical formation of vesical adenocarcinomas, including signet ring cell carcinomas. The expression of both pS2 and MUC5AC in variants of urothelial carcinomas with a glandular differentiation and an extracellular mucus production support the concept that adenocarcinomas may histogenetically develop from preexistent TCC. Adenocarcinomas which secrete the pS2 peptide and the MUC5AC glycoprotein are proposed to be subclassified as adenocarcinomas of the intestinal type, as distinguished from those of the common type lacking an expression. The tumor suppressor genes showed a loss of protein expression in adenocarcinomas, ranging from 54.5% (14-3-3 sigma), to 31.8 (PTEN), 27.3% (SYK) and 18.2% (maspin). Similar expression profiles in the coexistent urothelial carcinomas argue against a specific involvement of these genes during the morphogenesis of adenocarcinomas.
- PublicationOpen AccessUnique expression profiles of mucin proteins in interstitial pneumonia-associated lung adenocarcinomas(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2019) Tateishi, Yoko; Kataoka, Toshiaki; Okudela, Koji; Nakashima, Yu; Mitsui, Hideaki; Matsumura, Mai; Umeda, Shigeaki; Arai, Hiromasa; Baba, Tomohisa; Suzuki, Takehisa; Koike, Chihiro; Tajiri, Michihiko; Takemura, Tamiko; Ogura, Takashi; Masuda, Munetaka; Ohashi, KenichiIn order to clarify idiopathic interstitial pneumonia (IIP)-associated lung adenocarcinoma (LADC), we herein focused on the expression profiles of mucin proteins, the most common cellular differentiation markers. The expression of the mucin (MUC) 1, MUC2, MUC3B, MUC4, MUC5AC, MUC5B, MUC6, MUC7, MUC9, and MUC21 proteins was examined immunohistochemically and their levels were semi- quantified in 80 IIP-associated LADCs and 106 non-IIP LADCs. LADCs were divided into low and high expressers based on thresholds obtained from the receiver operating characteristic (ROC) curves of each mucin protein. Low expressers of MUC1, MUC7, and MUC21 and high expressers of MUC4, MUC5AC, MUC5B, and MUC9 were dominant in the IIP group. Multivariate analyses confirmed that the correlations between mucin expression profiles and IIP-associated LADCs were independent of putative confounding factors, such as smoking, gender, histological types, and cytological types. Thus, the expression profiles of these mucin proteins significantly differed between the IIP and non-IIP groups. IIP-associated LADCs appear to have unique cellular differentiation features and they may develop through a distinct histogenetic pathway. This is the first study to demonstrate that IIP-associated LADCs have unique mucin expression profiles.