Department of Pathology and Laboratory Sciences, Royal University Hospital, Saskatoon, SK, Canada.
World J Surg Oncol. 2010 Feb 12;8:10. doi: 10.1186/1477-7819-8-10.
Male breast cancer (MBC) is a rare, yet potentially aggressive disease. Although literature regarding female breast cancer (FBC) is extensive, little is known about the etiopathogenesis of male breast cancer. Studies from our laboratory show that MBCs have a distinct immunophenotypic profile, suggesting that the etiopathogenesis of MBC is different from FBCs. The aim of this study was to evaluate and correlate the immunohistochemical expression of cell cycle proteins in male breast carcinoma to significant clinico-biological endpoints.
75 cases of MBC were identified using the records of the Saskatchewan Cancer Agency over 26 years (1970-1996). Cases were reviewed and analyzed for the immunohistochemical expression of PCNA, Ki67, p27, p16, p57, p21, cyclin-D1 and c-myc and correlated to clinico-biological endpoints of tumor size, node status, stage of the disease, and disease free survival (DFS).
Decreased DFS was observed in the majority of tumors that overexpressed PCNA (98%, p = 0.004). The overexpression of PCNA was inversely correlated to the expression of Ki67 which was predominantly negative (78.3%). Cyclin D1 was overexpressed in 83.7% of cases. Cyclin D1 positive tumors were smaller than 2 cm (55.6%, p = 0.005), had a low incidence of lymph node metastasis (38.2%, p = 0.04) and were associated with increased DFS of >150 months (p = 0.04). Overexpression of c-myc (90%) was linked with a higher incidence of node negativity (58.3%, p = 0.006) and increased DFS (p = 0.04). p27 over expression was associated with decreased lymph node metastasis (p = 0.04). P21 and p57 positive tumors were related to decreased DFS (p = 0.04). Though p16 was overexpressed in 76.6%, this did not reach statistical significance with DFS (p = 0.06) or nodal status (p = 0.07).
Aberrant cell cycle protein expression supports our view that these are important pathways involved in the etiopathogenesis of MBC. Tumors with overexpression of Cyclin D1 and c-myc had better outcomes, in contrast to tumors with overexpression of p21, p57, and PCNA with significantly worse outcomes. P27 appears to be a predictive marker for lymph nodal status. Such observation strongly suggests that dysregulation of cell cycle proteins may play a unique role in the initiation and progression of disease in male breast cancer. Such findings open up new avenues for the treatment of MBC as a suitable candidate for novel CDK-based anticancer therapies in the future.
男性乳腺癌（MBC）是一种罕见但具有潜在侵袭性的疾病。尽管有关女性乳腺癌（FBC）的文献很多，但对男性乳腺癌的病因发病机制知之甚少。我们实验室的研究表明，MBC 具有独特的免疫表型特征，这表明 MBC 的病因发病机制与 FBC 不同。本研究旨在评估和比较男性乳腺癌中细胞周期蛋白的免疫组织化学表达与重要的临床生物学终点的相关性。
使用萨斯喀彻温癌症机构 26 年来的记录（1970-1996 年），确定了 75 例 MBC 病例。对病例进行了复习和分析，以检测 PCNA、Ki67、p27、p16、p57、p21、cyclin-D1 和 c-myc 的免疫组织化学表达，并与肿瘤大小、淋巴结状态、疾病分期和无病生存（DFS）等临床生物学终点相关。
大多数过度表达 PCNA 的肿瘤观察到 DFS 降低（98%，p=0.004）。PCNA 的过度表达与 Ki67 的表达呈负相关，Ki67 的表达主要为阴性（78.3%）。Cyclin-D1 在 83.7%的病例中过表达。Cyclin-D1 阳性肿瘤小于 2cm（55.6%，p=0.005），淋巴结转移发生率低（38.2%，p=0.04），DFS 超过 150 个月的比例较高（p=0.04）。c-myc 的过度表达（90%）与淋巴结阴性率较高（58.3%，p=0.006）和 DFS 增加（p=0.04）有关。p27 的过表达与淋巴结转移减少有关（p=0.04）。p21 和 p57 阳性肿瘤与 DFS 降低有关（p=0.04）。尽管 p16 的过度表达率为 76.6%，但与 DFS（p=0.06）或淋巴结状态（p=0.07）无统计学意义。
细胞周期蛋白表达异常支持我们的观点，即这些是男性乳腺癌发病机制中的重要途径。与过度表达 p21、p57 和 PCNA 的肿瘤相比，过度表达 Cyclin D1 和 c-myc 的肿瘤预后更好。p27 似乎是预测淋巴结状态的标志物。这些观察结果强烈表明，细胞周期蛋白的失调可能在男性乳腺癌的发生和发展中发挥独特作用。这些发现为男性乳腺癌的治疗开辟了新的途径，作为未来基于 CDK 的新型抗癌治疗的合适候选药物。
