Histology and histopathology Vol.27, nº 2 (2012)
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- PublicationOpen AccessSynchronous and metachronous multiple gastrointestinal stromal tumors(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Xu, Chen; Liu, Ya-Lan; Yu, Hong-Yu; Hou, Ying-Yong; Lu, Shao-Hua; Zhao, Li-Jun; Zhou, Yang; Shi, Yuan; Tan, Yun-Shan; Zhu, Xiong-ZengBackground & Aims: Sporadic multiple gastrointestinal stromal tumors (GISTs) are rare events especially those developed metachronously. This study aimed to investigate the clinico-pathologic and genetic features defining multiple GISTs. Methods: 624 cases of GISTs were retrieved for retrospective review. 15 cases were identified as multiple GISTs including 13 synchronous and 2 metachronous ones. 32 tumors and 15 normal tissues were obtained from these cases each containing 2-3 tumor nodules and the genomic DNA was extracted for mutational analysis of KIT and PDGFRA genes. The associated patients were recruited for clinical follow-up studies, including 5 males and 10 females at 49 to 84 years of age. Results: Multiple GISTs comprised of 2.4% of GIST cases in our consecutive series. Twenty-six tumors showed mutations at KIT gene in exon 11 and one at PDGFRA gene in exon 18. In seven synchronous cases, different tumors from the same patients displayed different genotypes of KIT or PDGFRA, suggesting their polyclonal origin. In the two multiple GISTs occurring metachronously, the tumors from each patient showed different KIT mutations, suggesting that the second tumors were not the relapse or metastasis of the primary GISTs. Conclusions: Based on types of KIT or PDGFRA mutations and other pathological features, multiple primary GISTs can be differentiated from multiple GISTs resulting from recurrence or metastasis of a single primary tumor. Unlike recurrence or metastasis of GISTs that are malignant, most multiple GISTs are mostly benign and do not require aggressive adjuvant therapy. Therefore, correct diagnosis is critical for proper treatment
- PublicationOpen AccessThrombospondin-1 expression in breast cancer: prognostic significance and association with p53 alterations, tumour angiogenesis and extracellular matrix components(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Ioachim, E.; Damala, K.; Tsanou, E.; Briasoulis, E.; Papadiotis, E.; Mitselou, Antigony; Charchanti, A.; Doukas, M.; Lampri, L.; Arvanitis, D.L.Thrombospondin (TSP-1) is a 450-kd adhesive glycoprotein that was initially discovered in platelets and subsequently in a variety of cell types. Several reports suggest that TSP-1 possesses tumour suppressor function, through its ability to inhibit tumour neovascularization. In this study we investigated tissue sections from 124 breast carcinomas for the immuno-histochemical expression of TSP-1 protein and its relationship to several clinicopathological parameters. The possible relationship to hormone receptors content, p53 protein, proliferation associated indices, angiogenesis, VEGF expression and extracellular matrix components (tenascin, fibronectin, laminin, collagen type IV and syndecan-1) was also estimated. TSP-1 was detected in the perivascular tissue, at the epithelial-stromal junction, in the stroma and in the tumour cells. High tumour cell TSP-1 expression was observed in 9.7%, moderate in 17.7%, mild in 10.5%, while 62.1% of the cases were negative for TSP-1 expression. The survival analysis showed an increased risk of recurrence associated with low TSP-1 tumour cell expression. High stromal TSP-1 expression was observed in 3.2% of the cases, moderate in 3.3%, mild in 27.4%, while 63.6% of the cases showed absence of TSP-1 expression. This expression was higher in invasive lobular type of breast cancer and inversely correlated with the lymph node involvement and the estrogen receptor content. Stromal TSP-1 expression was also positively correlated with extracellular matrix components expression, tenascin, fibronectin, collagen type IV, laminin, and syndecan-1. The relationship of TSP-1 expression with tumor angiogenesis, growth fraction and p53 protein expression was not significant. Our data suggest that TSP-1 expression seems to be associated with favorable biological behavior and may have clinical value in terms of predicting the risk of recurrence. In addition, TSP-1 might not be a direct anti-angiogenic factor, although it seems to be implicated in the remodeling of breast cancer tissue through interaction with other extracellular matrix components
- PublicationOpen AccessThe incidence and clinical significance of lymph node micrometastases determined by immunohistochemical staining in stage I - lymph node negative endometrial cancer(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) McCoy, Amy; Finan, Michael A.; Boudreaux, F.T.; Tucker, J. Alan; Lazarchick, John J.; Donnell, Robert M.; Rocconi, Rodney P.Objective: Determine the incidence and clinical relevance of lymph node micrometastases found with immunohistochemical (IHC) staining in patients diagnosed with stage I lymph node-negative endometrial adenocarcinoma. Methods: Eligible patients with endometrioid-type histology and negative lymph nodes by H&E were identified by a computerized database. After histologic confirmation, all paraffin-embedded pathologic specimens were freshly sliced and stained with IHC stains for pancytokeratin. Slides were interpreted by two pathologists and positive IHC staining for micrometastases was defined as positive staining of cells <2 mm in greatest dimension. Patient demographics, clinicopathologic factors, and follow-up data were abstracted. Results: Fifty-one patients were included in our study. Most patients had stage IA (84%) tumors of grade 2/3 histology (51%), and 11 patients (22%) received adjuvant therapy. Mean number of lymph nodes was 12.2 per patient. Of 151 lymph node paraffin blocks evaluated for pancytokeratin, only two (1.3%) had IHC-positive micrometastases. The two lymph node-positive results occurred in separate patients, leading to 3.9% of all patients in our cohort. Both micrometastatic lymph node-positive patients had adjuvant radiation therapy for uterine high-risk factors and are currently without evidence of disease at 15 and 16 months, respectively. Three lymph node-negative patients (6.1%) have developed recurrences within a median follow-up of 15 months. Conclusion: The incidence of IHC stain-positive micrometastases in H&E-negative lymph nodes is low in surgically staged endometrial cancer and does not justify routine IHC staining. Additionally, as little evidence exists to support the clinical significance of IHC-stained micrometastases in endometrial cancer, further study is warranted
- PublicationOpen AccessLess gelatinases is associated with apolipoprotein E accumulation in glomerulosclerosis rats(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Zhou, Tian-Biao; Qin, Yuan-Han; Lei, Feng-Ying; Su, Li-Na; Zhao, Jan-Jun; Huang, Wei-FangBackground: Gelatinases include matrix metalloproteinase-2 (MMP-2) and matrix metallo-proteinase-9 (MMP-9). The abnormal expressions of gelatinases are implicated in the pathogenesis of extracellular matrix (ECM) accumulation. Apolipo-protein E (apoE) is an important plasma protein in cholesterol homeostasis and plays a key role in the progression of glomerulosclerosis (GS). We conducted this investigation to explore whether gelatinases were associated with the apoE accumulation in the pathological process of GS. Methods: 40 Wistar rats were divided into two groups at random: sham operation group (SHO) and glomerulosclerosis model group (GS); n=20, respectively. The disease of GS was established by uninephrectomy and adriamycin (5 mg/kg) injection. At the end of 13 weeks, the 20 rats in each group were killed and the relevant samples were collected and measured. Results: Serum total protein (TP) and serum albumin (Alb) in GS group were reduced compared to those of the SHO group (P<0.01). Compared with the SHO group, values of 24-hour urine total protein (24UTP), 24-hour urine excretion for albumin (24Ualb), blood urea nitrogen (BUN), serum creatinine (Scr) and glomerulosclerosis index (GSI) in GS group were significantly increased (P<0.01). The protein of MMP-2 or MMP-9 in the glomerulus, and mRNA expression of MMP-2 or MMP-9 in renal tissue were reduced when compared with those in SHO (P<0.01). Protein expressions of apoE, collagen IV (Col-IV), fibronectin (FN), α-smooth muscle actin (α-SMA) and transforming growth factor-ß1 (TGF-ß1) in the glomerulus and expression of apoE mRNA in renal tissue were significantly up-regulated in GS group when compared with those in the SHO group (P<0.01). Conclusions: Lower expression of gelatinases is associated with the increased expression of apoE in the glomerulus, and increases the accumulation of ECM and takes part in the pathological change of GS.
- PublicationOpen AccessLocal identification of porcine haptoglobin in salivary gland and diaphragmatic muscle tissues(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Gutiérrez Montes, Ana María; Yelamos, J.; Pallarés Martínez, Francisco José; Gómez Laguna, J.; Cerón Madrigal, José JoaquínIn order to clarify the origin of the haptoglobin (Hp) quantified in saliva and meat juice samples, the extrahepatic localization of Hp in salivary gland and in diaphragmatic muscle, as part of the systemic acute phase response in pigs, was studied by immunohistochemistry. For this purpose a specific monoclonal antibody (mAb) produced by immunising mice with purified porcine Hp was used. Reactivity of the mAb was assessed by direct ELISA and by western blot, which showed the ability and specificity of the mAb to identify porcine haptoglobin as a purified antigen or in porcine serum in a native or denatured but non-reduced state. Five healthy and five diseased pigs were sampled at slaughter for serum and tissue procurement. Hepatic immunohistochemical analysis was used as control of the acute phase reaction status. In the liver, cell immunostaining revealed a perinuclear, cytoplasmic localization of Hp within hepatocytes, following mainly a periacinar pattern. Extrahepatic immunohistochemical analysis revealed positive cells in the glandular acini and duct epithelial cells of the salivary gland and intrasarcoplasmic immunolabelling of random diaphragmatic myofibers. A possible role of both salivary gland and diaphragmatic muscle on local Hp production could be postulated based on the present immunohistochemical study, which supports the concept that other cells besides hepatocytes may have the potential to produce Hp in the pig
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