Abstract

Abstract Objective: Gall bladder cancer (GBC) is the commonest biliary tract cancer worldwide. It is the commonest gastro-intestinal cancer in women in northern India; it is common in Native American Indian people also. GBC is usually associated with gall stones (GS) and chronic cholecystitis (CC); xantho-granulomatous cholecystitis (XGC) is a variant of CC. Most patients with GBC are diagnosed at an advanced stage and overall prognosis is poor. Prophylactic cholecystectomy in patients with asymptomatic GS can prevent GBC, but it can not be advised in everyone with GS. There is a need to identify some bio-markers for early diagnosis and prevention GBC. Materials and Methods: We evaluated the immuno-histo-chemical (IHC) expression of carcino-embryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in histo-pathologically confirmed GBC (n=51), CC (n=68), XGC (n=42) and normal GBs removed during operations on bile duct, liver and pancreas (n=10). IHC was performed using mouse monoclonal primary antibodies for CEA (Clone II-7, 1:100, Dako) and CA 19.9 (Clone 116-NS-19-9, 1:100, Dako) using labeled Streptavidin Biotin Peroxidase method. Intensity of staining was recorded as absent (0), mild (1), moderate (2) and intense (3) while the percentage of nuclei stained were scored as absent/<5% (0), >5 <10% (1), 10–50% (2) and >50% (3). The total score was calculated by adding the intensity score and the percentage score and ranged from 0–6. A score of ≥3 was considered as positive. Results: CEA expression was present in 42/51 (82%) of GBC - it was apical in 13, focal cytoplasmic in 15 and diffuse cytoplasmic in 14 cases. CEA expression was seen in 18/68 (27%) of CC - it was apical in all 18 with focal cytoplasmic in 9. CEA expression was seen in 4/42 (10%) of XGC - it was apical in all 4; many cases with XGC, however, did not have epithelium. All 10 normal GBs showed apical CEA expression. Diffuse cytoplasmic staining of CEA was seen in only GBC and was not seen in CC, XGC and normal GBs. CA 19-9 expression was seen in 38/51 (75%) of GBC - all cytoplasmic; all 13 CA19-9 negative GBCs were high grade on histopathology. All CC, XGC and normal GBs showed apical and diffuse cytoplasmic positivity for CA 19-9. Conclusion: Tumor markers such as CEA and CA 19-9 can be used to screen patients with asymptomatic GS to identify a sub-group with higher risk to develop GBC who can then be offered prophylactic cholecystectomy for secondary prevention of GBC. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A26.

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