Aldovini Daniela, Demichelis Francesca, Doglioni Claudio, Di Vizio Dolores, Galligioni Enzo, Brugnara Sonia, Zeni Bruna, Griso Claudia, Pegoraro Cristina, Zannoni Marina, Gariboldi Manuela, Balladore Emanuela, Mezzanzanica Delia, Canevari Silvana, Barbareschi Mattia
Department of Pathology, S. Chiara Hospital, Trento, Italy.
Int J Cancer. 2006 Oct 15;119(8):1920-6. doi: 10.1002/ijc.22082.
Currently available clinico-pathologic criteria provide an imperfect assessment of outcome for patients with advanced epithelial ovarian cancer (EOC). Identification of prognostic factors related to tumor biology might improve this assessment. We investigated the prognostic significance of the melanoma cell adhesion molecule (M-CAM) in EOC. Using the same antibody, M-CAM expression was tested by Western blotting in protein extracts and by immunohistochemestry in tissue microarrays generated from 133 consecutively resected, well characterized EOC samples. Fisher test, Kaplan-Meier method and Cox proportional hazards analysis were used to relate M-CAM expression to clinico-pathological variables and to time to progression (TTP) and overall survival (OS). In vitro biochemical analysis showed a progressively increased M-CAM expression from normal to malignant cells. M-CAM protein, detected immunohistochemically, was significantly associated with advanced tumor stage, serous and undifferentiated histotype, extent of residual disease and p53 accumulation. Presence or absence of M-CAM significantly divided patients according to their TTP (median, 22 vs. 79 months, respectively; log-rank p = 0.001) and OS (median, 42 vs. 131 months, respectively; log-rank p = 0.0003). In the subgroup of advanced stage patients who achieved complete response after front-line treatment, M-CAM expression and absence of residual disease were significantly associated with shorter TTP (p = 0.003, HR 5.25, 95% Cl 1.79-15.41 and p = 0.011, HR 3.77, 95% Cl 1.36-10.49 respectively) at the multivariate level. In the same sub-group of patients, M-CAM expression remained the only parameter significantly associated with OS (p = 0.005, HR 3.35, 95% Cl 1.42-6.88). M-CAM is a marker of early relapse and poorer outcome in EOC. In particular, M-CAM expression identifies a subgroup of front-line therapy-responding patients who undergo dramatic relapses, thus helping to better select patients who might benefit from new/alternative therapeutic modalities.
目前可用的临床病理标准对晚期上皮性卵巢癌（EOC）患者的预后评估并不完善。识别与肿瘤生物学相关的预后因素可能会改善这种评估。我们研究了黑色素瘤细胞粘附分子（M-CAM）在EOC中的预后意义。使用相同的抗体，通过蛋白质提取物的蛋白质印迹法和来自133例连续切除、特征明确的EOC样本的组织微阵列的免疫组织化学法检测M-CAM表达。采用Fisher检验、Kaplan-Meier法和Cox比例风险分析将M-CAM表达与临床病理变量以及进展时间（TTP）和总生存期（OS）相关联。体外生化分析显示从正常细胞到恶性细胞M-CAM表达逐渐增加。免疫组织化学检测到的M-CAM蛋白与晚期肿瘤分期、浆液性和未分化组织学类型、残留疾病范围和p53积累显著相关。M-CAM的存在与否根据患者的TTP（中位数分别为22个月和79个月；对数秩检验p = 0.001）和OS（中位数分别为42个月和131个月；对数秩检验p = 0.0003）显著区分患者。在一线治疗后达到完全缓解的晚期患者亚组中，在多变量水平上，M-CAM表达和无残留疾病与较短的TTP显著相关（分别为p = 0.003，HR 5.25，95%CI 1.79 - 15.41和p = 0.011，HR 3.77，95%CI 1.36 - 10.49）。在同一患者亚组中，M-CAM表达仍然是与OS显著相关的唯一参数（p = 0.005，HR 3.35，95%CI 1.42 - 6.88）。M-CAM是EOC早期复发和较差预后的标志物。特别是，M-CAM表达识别出一组对一线治疗有反应但经历显著复发的患者，从而有助于更好地选择可能从新的/替代治疗模式中获益的患者。
