Thi4e Expressions Of Erkl/2,P16^INK4a,p-gp In Cervical Adenocarcinoma And Its Relation To Chemoresistance And Clinical Significance

Objective:Chemotherapy is an important part in the regular management of cervicaladenocarcinoma. Drug resistance appears as the biggest obstacle to successfulchemotherapy and has becoming the leading cause of relapse and therapeutic failurein cervical adenocarcinoma. This study aims to explore relation between theexpressions of extracellular signal-regulated kinase1/2(ERK1/2), P16^INK4a,P-glycoprotein (P-gp) and the chemoresistance of cervical adenocarcinoma, and toinvestigate their association with the3-year survival rate of these patients.Methods:1. Collecting39paraffin-embedded biopsy specimens of stagingⅠb1～Ⅱbcervical adenocarcinoma patients who had received two cycles of platinum-basedchemotherapy. According to the Response Evaluate Criteria in Solid Tumor (2000),these39patients were classified into two groups: chemothsensitive group (14patients)and chemoresistant group (25patients).2. Using immunohistochemistry (PV-9000) to detect the expressions of ERK1/2,P16^INK4aand P-gp in the biopsy specimens of cervical adenocarcinoma.Immunohistochemical staining intensities were classified into four grades:-,+,++,+++. And "++,+++" were defined as high expression.3. Analyzing the expressions ERK1/2, P16^INK4aand P-gp in the biopsyspecimens of cervical adenocarcinoma and their differences between thechemosensitive group and chemoresistant group.4. Analyzing the correlation among the expressions ERK1/2, P16^INK4aand P-gpand exploring their association with the chemoresistance of cervical adenocarcinoma.5. Analyzing the relation between the expressions of ERK1/2, P16^INK4aand P-gpand the3-year survival rate of the patients with cervical adenocarcinoma.Result:1. The expression rates of ERK1/2, P16^INK4aand P-gp in the biopsy specimensof cervical adenocarcinoma are89.7%(35/39),82.1%(32/39) and84.6%(33/39) respectively.2. The highly expressed rates of ERK1/2in chemoresistant group andchemosensitive group are72.0%(18/25) and35.7%(5/14) respectively. And there isstatistical significance between them (P<0.05); The highly expressed rates ofP16^INK4ain chemoresistant group and chemosensitive group are76.0%(19/25) and42.9%(6/14) respectively. While the difference between them is not statisticallysignificant (P>0.05); The highly expressed rate of P-gp is72.0%(18/25) inchemoresistant group which is obviously higher than that of chemosensitive group(35.7%(5/14)), and this difference is statistically significant(P<0.05).3. The expression of ERK1/2is positively correlated with that of P16Ink4(r=0.571, P<0.001), and the expression of ERK1/2is positively correlated with thatof P-gp (r=0.364, P<0.05), while there is no obvious correlation between theexpression of P16^INK4aand the expression of P-gp (r=0.254, P>0.05).4. The3-year survival rates of for ERK1/2highly expressed patients and lowlyexpressed patients were60.9%and93.8%, and there is statistical significancebetween them (P<0.05), while there is no statistical significance between the3-yearsurvival rates of the patients with different expressions of P16^INK4aand P-gp(P>0.05).Conclusions1. The high expression of ERK1/2may associate with the chemoresistance ofcervical adenocarcinoma.2. The high expression of P-gp correlate with the chemoresistance of cervicaladenocarcinoma.3. The expression of ERK1/2is related with the prognosis of cervicaladenocarcinoma patients.4. The role of ERK1/2and P16^INK4ain chemoresistance of cervicaladenocarcinoma is to be further explored in prospective study with more samples.