Lee C S
Department of Pathology, University of Melbourne, Australia.
Cancer. 1996 Nov 1;78(9):1881-7. doi: 10.1002/(sici)1097-0142(19961101)78:9<1881::aid-cncr6>3.0.co;2-i.
Cell proliferative activity is an important indicator of growth and behavior of various human tumors. Immunostaining of tissue sections with proliferating cell nuclear antigen (PCNA) and Ki-67 antibodies appears to be reliable in the assessment of tumor cell proliferation. This study examined differences in cell kinetics between neoplastic and nonneoplastic lesions of the gallbladder and biliary tract using an antibody against PCNA and Ki-67.
There were a total of 27 cancer cases comprising patients with invasive carcinoma of the gallbladder (n = 13), common bile duct (n = 5) and ampulla of Vater (n = 8). Cases of chronic cholecystitis (n = 11) from the nonneoplastic group; carcinoma in situ (CIS) of the gallbladder (n = 4) and ampulla (n = 6) from the noninvasive group. Cell cycle activity was determined in sections of routinely formalin fixed, paraffin processed, biopsy material using immunohistochemical stains for the monoclonal PCNA, PC10, KI-67, and MIB-1. The expression of PCNA and MIB-1 in these conditions was determined by calculating the percentage of cell nuclei that stained positively to obtain the PCNA and MIB-1 indices, respectively.
The PCNA and MIB-1 indices in chronic cholecystitis were significantly lower than those obtained in both moderately and poorly differentiated adenocarcinoma of the gallbladder (P < 0.001). Similarly, cases of ampullary and gallbladder CIS had significantly lower PCNA and MIB-1 indices than the invasive carcinoma cases (P < 0.001). There was a strong correlation between PCNA and MIB-1 expression (r = 0.828, r2 = 0.686; P = 0.001), although the PCNA index was generally higher than that of MIB-1. The poorly differentiated adenocarcinomas of the gallbladder had higher mean PCNA and MIB-1 indices but reduced patient survival when compared with the moderately differentiated carcinomas.
In conclusion, gallbladder, ampulla, and common bile duct carcinomas have significantly higher PCNA and MIB-1 indices than CIS and nonneoplastic lesions. Because tumors with higher PCNA or MIB-1 indices are associated with a poorer prognosis, both PCNA and MIB-1 may be useful markers of tumor cell proliferative activity and biologic behavior in gallbladder, ampullary, and common bile duct carcinomas.
细胞增殖活性是各种人类肿瘤生长和行为的重要指标。用增殖细胞核抗原（PCNA）和Ki-67抗体对组织切片进行免疫染色，在评估肿瘤细胞增殖方面似乎是可靠的。本研究使用抗PCNA和Ki-67抗体，检测胆囊和胆道肿瘤性病变与非肿瘤性病变之间的细胞动力学差异。
共有27例癌症病例，包括胆囊浸润癌患者（n = 13）、胆总管癌患者（n = 5）和壶腹癌患者（n = 8）。非肿瘤组有11例慢性胆囊炎病例；非侵袭组有胆囊原位癌（CIS）病例（n = 4）和壶腹原位癌病例（n = 6）。使用针对单克隆PCNA、PC10、KI-67和MIB-1的免疫组织化学染色，在常规福尔马林固定、石蜡包埋的活检材料切片中测定细胞周期活性。通过计算细胞核阳性染色的百分比来确定这些情况下PCNA和MIB-1的表达，分别获得PCNA和MIB-1指数。
慢性胆囊炎中的PCNA和MIB-1指数显著低于胆囊中、低分化腺癌的指数（P < 0.001）。同样，壶腹和胆囊CIS病例的PCNA和MIB-1指数显著低于浸润癌病例（P < 0.001）。PCNA和MIB-1表达之间存在强相关性（r = 0.828，r2 = 0.686；P = 0.001），尽管PCNA指数通常高于MIB-1指数。与中分化癌相比，胆囊低分化腺癌的平均PCNA和MIB-1指数更高，但患者生存率更低。
总之，胆囊癌、壶腹癌和胆总管癌的PCNA和MIB-1指数显著高于CIS和非肿瘤性病变。由于PCNA或MIB-1指数较高的肿瘤预后较差，PCNA和MIB-1可能都是胆囊癌、壶腹癌和胆总管癌肿瘤细胞增殖活性和生物学行为的有用标志物。
