Abstract
Gallbladder cancer (GBC) is an aggressive and highly lethal disease with relatively low global incidence, but one that constitutes a major health problem in Asian and Latin American countries, particularly in Chile. The identification of new tumor-associated markers with potential prognosis value is required for GBC clinical practice. Using immunohistochemistry/tumor tissue microarray, we evaluated the expression of 17 gastrointestinal tumor-associated protein markers (CK7, CK17, CK19, CK20, CKLMW, CKHMW, MUC1, MUC2, MUC5AC, MUC6, CA125, CD10, CEA, vimentin, villin, claudin-4, and CDX2) in primary gallbladder adenocarcinomas from 180 Chilean patients and analyzed potential associations with their pathological and clinical characteristics. Younger female patients with well- to moderately differentiated tumors had a better prognosis than that of older female or male patients with tumors with a similar tumor differentiation grade. Among all analyzed markers, MUC6 expression was associated with better prognosis in patients with well- to moderately differentiated tumors, whereas CK17 or CD10 was associated with worse prognosis in patients with poorly differentiated tumors. In addition, the MUC6+CK17– expression pattern was strongly associated with better prognosis in patients with well- to moderately differentiated tumors, whereas patients with poorly differentiated tumors and with the CK17+CD10+ expression pattern showed worse prognosis. Our results suggest that tumor MUC6, CK17, and CD10 can be considered as potential prognosis markers for GBC.
Highlights
Gallbladder cancer (GBC) is the most frequent malignancy of the biliary tract and the fifth most common digestive neoplastic disease [1,2]
In a cohort of 180 Chilean patients with primary gallbladder adenocarcinoma, we evaluated the expression of 17 gastrointestinal tumor-associated protein markers consisting of six cytokeratins (CK7, Cytokeratin 17 (CK17), CK19, CK20, CKLMW, and CKHMW), five mucins (MUC1, MUC2, MUC5AC, MUC6, and Cancer antigen-125 (CA125)), two glycoproteins (CD10 and carcinoembryonic antigen (CEA)), two cytoskeleton-associated proteins, one tight junction protein (Claudin4), and one transcription factor (CDX2)
Our results showed that MUC6 tumor expression was associated with a better prognosis in patients with well- to moderately differentiated tumors, whereas CK17 or CD10 tumor expression was associated with worse prognosis in patients with poorly differentiated tumors
Summary
Gallbladder cancer (GBC) is the most frequent malignancy of the biliary tract and the fifth most common digestive neoplastic disease [1,2]. The prognosis of GBC is poor, with a median overall survival (OS) time of 3–11 months and a five-year survival rate ranging from 4% to 60%, depending on disease stage and tumor receptibility. This is mainly due to the aggressive behavior of the tumor cells and its nonspecific symptoms, leading to late clinical manifestation and, diagnosis at an advanced stage [3]. Other risk factors associated with GBC carcinogenesis are, for example, gender (women have two to six times more chances to develop GBC than men), obesity, congenital developmental abnormalities, sedentary behavior, gallbladder chronic infection and inflammation, ethnicity, and advanced age [7,8,9]. Adenocarcinoma is the most common histologic type, accounting for 98% of all gallbladder tumors
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