Histology and histopathology Vol.37, nº7 (2022)
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- PublicationOpen AccessHistological diversity of anti-PD1-induced colitis(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Sakellariou, Stratigoula; Papathanasiou, Evgenia; Perdiki, Marina; Sotiropoulou, Maria; Zampeli, Evangelia; Michopoulos, Spyros; Bamias, Giorgos; Delladetsima, IoannaAim. Histological data on anti-PD1- associated colitis are limited, while the colitis subtypes are still not clearly defined and different terms are being used. The aim of the study was to explore the histopathology of anti-PD1-induced colitis. Methods and Results. Colonic biopsies from 9 patients under anti-PD1 agents presenting diarrhea were examined. Histological evaluation revealed colitis of mild to moderate severity in almost all cases. Four distinct dominant histological patterns were identified with nearly the same incidence: Ulcerative colitis (UC)- like (n=2), GVHD-like (n=2), collagenous-like (n=3) and a mixed colitis pattern combining features of microscopic and UC-like colitis (n=2). The latter was additionally characterized by high crypt epithelium apoptosis and cryptitis with mixed inflammatory infiltrate. Thickening of the subepithelial band of collagen, detachment of the surface epithelium and increased apoptosis of the crypt epithelium were commonly encountered features, irrespective of colitis subtype. CD4/CD8 ratio was lower in the “combined” and higher in the GVHD-like subtype. Conclusions. Anti-PD1-induced colitis is expressed by different patterns of injury which share distinct histological hallmarks harboring diagnostic value, while a “combined” colitis subtype is being established. The histological alterations are indicative of mucosa barrier damage after ant-PD1 treatment and its participation in the pathogenetic process
- PublicationOpen AccessThe clinicopathological and prognostic significances of LATS1 expression in breast cancer(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Zheng, Hua Chuan; Xiang, Li Wei; Cui, Zheng Guo; Xue, Hang; E, Ying; Zhao, Ming ZhenAim. Large tumor suppressor gene 1 (LATS1) belongs to the PKA/PKG/PKC serine/threonine kinase subfamily of the Hippo signaling pathway and inactivates nuclear co-activators YAP1 and WWTR1 by phosphorylation. This study aimed to discern the clinicopathological and prognostic significances of LATS1 expression in breast cancer. Methods. We examined LATS1 expression in breast carcinogenesis and compared it with clinicopathological parameters and survival information of breast cancer patients using immunohistochemistry, western blotting, RT-PCR, and bioinformatics analysis. Results. LATS1 expression was downregulated in breast cancer at both mRNA and protein levels (P<0.05). LATS1 mRNA expression was negatively correlated with low ER and PR expression, aggressive subtypes (TNBC and HER2+ vs. luminal), and poor survival (P<0.05). Its protein expression was negatively linked to T stage, N stage, M stage, TNM stage, histological grade, PR status, and unfavorable prognosis (P<0.05). There was a positive correlationship between nuclar and cytoplasmic LATS1 expression in breast cancer (P<0.05). Conclusions. The downregulation of LATS1 expression plays a vital role in the carcinogenesis and progression of breast cancer. Thus, LATS1 loss was employed to indicate the aggressive behaviors and poor prognosis of breast cance
- PublicationOpen AccessThe expression of hydrogen sulfide-producing enzymes in primary and lung metastatic osteosarcoma(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Gong, Lihua; Sun, Xiaoqi; Zhang, Ming; Du, Junbao; Ding, Yi; Jin, HongfangBackground. Hydrogen sulfide (H2S) is a novel gas transmitter signaling molecule. H2S is synthesized by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MST). There have been no reports about the roles of these enzymes in osteosarcoma and its metastases. We detected H2S synthase expression levels in human primary osteosarcoma and lung metastatic osteosarcoma. Methods. Immunohistochemistry was performed in primary osteosarcoma (n=19), lung metastatic osteosarcoma (n=11), osteoblastoma (n=10) and bony callus (n=2). The expression of CBS, CSE, and MST was defined as negative, moderately positive and strongly positive. Results. MST staining was moderately to strongly positive in all cases. CSE staining was negative in 94.7% (18/19) of primary osteosarcoma cases and 90.9% (10/11) of lung metastatic osteosarcoma cases. CBS staining was strongly positive in 68.4% (13/19) of primary osteosarcoma cases, moderately positive in 15.8% (3/19) of cases, and negative in 15.8% (3/19) of cases. In lung metastatic osteosarcoma, the proportions of negative, moderately positive and strongly positive cases were 63.6% (7/11), 18.2% (2/11) and 18.2% (2/11), respectively. Conclusions. CBS and CSE expression, especially CSE expression, decreased in both primary osteosarcoma and lung metastatic osteosarcoma, which may suggest that CBS and CSE play roles in osteoblast cell malignant transformation and osteosarcoma progression. These enzymes could be used as new prognostic assessment factors and may represent new therapeutic targets for osteosarcoma and metastasis prevention
- PublicationOpen AccessThe clinicopathological and prognostic characteristics of mucinous micropapillary carcinoma of the breast(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Sun, Yangyang; Gu, Wenxian; Wang, Gengfang; Zhou, XiaoliBackground. Mucinous micropapillary carcinoma (MMPC) is a unique subtype of breast cancer, and there is as yet no detailed report on the clinical characteristics of MMPC. Methods. MMPC, pure mucinous breast carcinoma (PMBC), and invasive micropapillary carcinoma (IMPC) samples were enrolled simultaneously, and immunohistochemistry analysis was performed to explore the clinicopathological attributes of MMPC. Moreover, survival analyses of MMPC were performed among the MMPC, PMBC, and IMPC groups and within the MMPC group. Results. The results showed that MMPC demonstrated distinct pathological features and that vascular invasion and lymph node metastasis were two significant clinical attributes of MMPC. MMPC leads to a shorter survival time than PMBC but an increased survival time compared to IMPC, while the tumor-nodemetastasis stage and lymph node metastasis were identified as two independent prognostic elements for disease-free survival in discerning the MMPC prognosis. Conclusions. The gathered data implied that further understanding and classification of MMPC may provide better individualized therapeutic strategies for MMPC treatment
- PublicationOpen AccessEvaluation of the multiple tissue factors in bone of primary osteoplasty and rhinoplasty in patients affected by cleft lip palate(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Buile, Dace; Pilmane, Māra; Akota, IlzeClefts of the lip and/or palate (CLP) are visible disruptions of standard facial structure. The aim of our study was to determine a relative number and appearance of the tissue factors in bone of patients with CLP during first time plastic alveolar osteoplasty or rhinoplasty. Immunohistochemistry was performed with matrix metalloproteinase-8 (MMP-8), matrix metalloproteinase9 (MMP-9), osteopontin (OPN), osteocalcin (OC), Runtrelated transcription factor 2 (Runx2), beta-defensin-2 (βdef-2), beta-defensin-3 (βdef-3), interleukin-1 alpha (IL-1α), and interleukin-10 (IL-10). The bone formation was observed by Masson-trichrome (Masson) staining. For the quantification of structures, the semi-quantitative census method was used. Spearman rank order correlation coefficient and Mann-Whitney U test were used for the statistical analysis. A significantly higher number of OPN positive osteocytes was observed in the CLP group when compared to the control group (p=0.002). The number of OC positive osteocytes (p=0.000) and βdef-2 positive osteocytes (p=0.003) was significantly lower in the CLP group in comparison to the control group. Strong, positive correlations between IL-10 and OC (rs=0.608; p=0.002), IL-1α and MMP-9 (rs=0.666; p=0.000), OPN and MMP-8 (rs=0.620; p=0.002) were detected in the CLP group. A tendency for the increased appearance of MMP-8, MMP-9 positive osteocytes of the patients with CLP, suggests elevated tissue remodelling properties. Increased appearance of OPN positive osteocytes in bone of the patients with CLP shows increased bone homeostasis based on seriously decreased mineralization, which may be a possible compensatory reaction to decreased quality of postsurgical bone.