ABSTRACT
Background: Mucins may show aberrant expression, localization, and/or glycosylation in multiple malignancies. However, information regarding expression of these mucins is mostly unknown in urothelial tumors. Aim: This study was conducted for examining the expressions of membrane associated and secreted mucin (MUC1) and a secreted gel-forming mucin (MUC2) in urothelial tumors of the urinary bladder. Subjects and Methods: Archival transurethral resection materials of 97 urothelial carcinoma cases were reexamined light microscopically and graded according to the 2004 WHO Classification. Pathological stage was given as pTa, pT1, and pT2. Demonstrative sections were recut for immunohistochemistry for MUC1 and MUC2. The results were statistically analyzed, and P < 0.05 was considered statistically significant. Results: The positivity for MUC1 and MUC2 was 89.7% and 44.3%, respectively. Independent from pathological stage of the tumor, MUC1 expression showed statistically significant correlation with tumor grade (P < 0.05). We did not find any correlation between pathological stage and MUC1 and MUC2 expression (P > 0.05). MUC1 staining pattern in papillary urothelial neoplasm of low malignant potential cases was more commonly apical and superficial (luminal cell layer only). Intermediate cells ± basal cells or isolated cells or islands of tumor cells with cytoplasmic and/or circumferential membrane positivity for MUC1 and MUC2 were more commonly observed in both low- and high-grade carcinomas. The difference between groups in terms of MUC1 and MUC2 staining was statistically significant (P < 0.05). Conclusions: The staining patterns of both mucins are different between urothelial papillary tumors and may be used to make a differentiation, especially for low-grade papillary urothelial lesions. This difference may also be important in the carcinomatous transformation of urothelial neoplastic and preneoplastic lesions.
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Background: The prognostic significance and clinico-pathological characterization of mucin (MUC) expression in non-small cell lung cancer (NSCLC) is controversial and little studied. Aims: This study aims at elucidating this issue on the largest and most detailed cohort so far. Settings and Design: We examined the expression of MUC 1, 2, 4, 5AC and 6 on 371, well documented, surgically resected NSCLC cases. Materials and Methods: Immunohistochemical results were correlated with several of our previously studied, relevant parameters on this cohort including a follow-up period of up to 20 years. An additional point we examined for practical reasons that has not been addressed so far, was the possible assistance of MUC expression for the differentiation between a primary lung adenocarcinoma and metastasis from a known pancreatobiliary primary tumor. Statistical Analysis Used: Cronbach's Alpha reliability correlation, Spearman's correlation, ANOVA means of comparison with additional Kruskall–Wallis H-test, and Kaplan–Meier survival analysis were employed as statistical analyses in this study. Results and Conclusions: MUCs were associated with histologic subtypes, tumor differentiation and members of the epidermal growth factor receptor signaling pathway, although they were not found to be significant for prognosis. Expression of MUC1 correlated with certain other markers and may point to a group of patients relevant for upcoming treatment strategies involving MUC1. According to our findings, we also recommend additional MUC5AC staining for a thyroid transcription factor 1-negative adenocarinoma in the lung for the differentiation of a possible metastasis in the presence of a pancreatic ductal adenocarcinoma.
ABSTRACT
Introducción: Las mucinas son glicoproteínas y desempeñan funciones biológicas. Diversas anormalidades genéticas y epgenéticas han sido descritas en el cáncer gástrico. El objetivo de la investigación fue observar la inmuno-expresión de mucinas en cánceres difusos e intestinales y las lesiones pre-neoplásicas limítrofes. Métodos: Se evaluaron 18 cánceres difusos (56.3%) y 14 intestinales (43.7%) y las lesiones precursoras adyacentes al cáncer gástrico. Se realizó inmunohistoquímica para los siguientes marcadores: MUC-1, MUC-2, MUC5-AC, MUC-6, HGM y CD10. Resultados: La inmune-expresiones fue: MUC-1 (54.5%), de los cánceres intestinales y (45.5%) de los cánceres difusos. MUC-2 (50%) de los cánceres difusos y (50%) de los cánceres del tipo intestinal. MUC-5AC (39.3%) del tipo difuso (60.7%) del tipo intestinal. HGM (37.5%) del tipo intestinal y (62.5%) del tipo difuso. MUC-6 (57.9%) del tipo difuso (42.1%) los del tipo intestinal. CD10 (55.6%) del tipo intestinal, y (44.4%) en los difusos.En las lesiones pre- cursoras adyacentes al cáncer gástrico la MUC-1 se inmunoexpresa en metaplasia intestinal (9.7%). MUC-2 (83.9%) en metaplasia intestinal. MUC5-AC (90,6%) en foveolas MUC-6 (100%) positiva en glándulas. CD10 (54.8%) positiva en metaplasia intestinal.HGM (75%) en foveolas y el (64.5%) en metaplasia intestinal. MUC-6 (100%) en glándulas profundas y (64,5%) en metaplasia intestinal. Las dis- plasias expresaron MUC-2 y MUC-5AC, en el 80% y 100% respectivamente. Conclusiones: La inmunotipificación del cáncer gástrico permitirá una clasificación más exacta de los tumores asi como la identificación de posibles dianas terapéuticas y su relación con factores genético y epigeneticos.
Introduction: Mucins are glycoproteins and has diverse biological roles. Epi-genetic abnormalities have been described in gastric cancer. The aim of the research was evaluate immunoexpression of mucins in diffuse and intestinal cancers and pre-neoplastic lesions. Methods: We evaluated 18 diffuse cancers (56.3%) and 14 intestinal (43.7%) and adjacent precursor lesions to gastric cancer immunohistochemical markers used was MUC-1, MUC-2-AC MUC5, MUC-6, and CD10 HGM. Results: The immuno-expression was: MUC-1 (54.5%), and intestinal cancers (45.5%) diffuse cancers. MUC-2 (50%) and diffuse cancers (50%) of cancers of the intestinal type. MUC-5AC (39.3%) diffuse type (60.7%) of intestinal type.HGM (37.5%) intestinal type (62.5%) in diffuse type. MUC-6 (57.9%) diffuse type (42.1%) in the intestinal type. CD10 (55.6%) in intestinal type, and (44.4%) in the diffuse type In adjacent precursor lesions to gastric cancer we observed MUC-1 in intestinal metaplasia (9.7%). MUC-2 (83.9%) in intestinal metaplasia. MUC5-AC (90.6%) in foveolasMUC-6 (100%) positive glands. CD10 (54.8%) positive in intestinal.HGM metaplasia(75%) and in foveolae (64.5%) in metaplasia intestinal. MUC-6 (100%) deep glands (64.5%) in metaplasia.intestinal. Dys- plasias expressed MUC-2 and MUC-5AC, 80% and 100% respectively. Conclusions: The gastric cancer immunotyping allow more accurate classification of tumors and the identification of potential therapeutic targets and its relationship with genetic and epigenetic factors.
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This review article describes morphological aspects, gene abnormalities, and mucin expression profiles in precursor lesions such as pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), and mucinous cystic neoplasm (MCN) of the pancreas, as well as their relation to pancreatic ductal adenocarcinoma (PDAC). The gene abnormalities in precursors of PDAC are summarized as follows: (1) KRAS mutation and p16/CDKN2A inactivation are early events whose frequencies increase with the dysplasia grade in both PanIN and IPMN; (2) TP53 mutation and SMAD4/DPC4 inactivation are late events observed in PanIN3 or carcinomatous change of IPMN in both PanIN and IPMN, although the frequency of the TP53 mutation is lower in IPMN than in PDAC; and (3) also in MCN, KRAS mutation is an early event whose frequency increases with the dysplasia grade, whereas TP53 mutation and SMAD4/DPC4 inactivation are evident only in the carcinoma. The mucin expression profiles in precursors of PDAC are summarized as follows: (1) MUC1 expression increases with the PanIN grade, and is high in PDAC; (2) the expression pattern of MUC2 differs markedly between the major subtypes of IPMN with different malignancy potentials (i.e., IPMN-intestinal type with MUC2+ expression and IPMN-gastric type with MUC2- expression); (3) MUC2 is not expressed in any grade of PanINs, which is useful for differentiating PanIN from intestinal-type IPMN; (4) de novo expression of MUC4, which appears to increase with the dysplasia grade; and (5) high de novo expression of MUC5AC in all grades of PanINs, all types of IPMN, MCN, and PDAC.