Hormone receptor expression of colorectal cancer diagnosed during the peri-partum period

Background Colorectal carcinoma (CRC) during the peri-partum period is challenging to diagnose due to the overlapping symptoms of CRC and pregnancy. This is the first case series to investigate clinicopathologic, hormonal and molecular features of CRC diagnosed during the peri-partum period. We hypothesized that advanced presentations of CRC could possibly be mitigated by pregnancy-related hormonal factors. Methods We conducted a retrospective review of five women diagnosed with CRC during the peri-partum period and studied the clinical and molecular features of their cancer. Results All patients presented with stage IV CRC at diagnosis; three had primary tumors in the rectum and two had primary tumors in the sigmoid colon. The liver was the most common metastatic site (three of five women). Immunohistochemistry stains were negative for estrogen receptors alpha (ERα) and beta (ERβ), and one tumor demonstrated low-level positivity for PR (1%). Formalin-fixed and paraffin-embedded (FFPE) biopsies from each case were tested with next-generation sequencing and found that all tumors were mismatch repair (MMR) proficient, and three harbored a KRAS mutation. Germline testing showed no predisposition to CRC; however, several somatic variants of undetermined significance (VUS) were identified. Discussion CRC in the peri-partum period poses significant risk factors for presentations with advanced disease due to diagnostic challenges. While our study provides no evidence that pathogenesis of CRC during pregnancy is driven by elevated estrogen and/or progesterone levels during pregnancy, additional putative etiologic factors, including placental growth factors, the immunosuppressive state of pregnancy and other physiologic processes during pregnancy, warrant future study.

背景 由于结直肠癌（CRC）和妊娠的症状有重叠，围产期的结直肠癌诊断具有挑战性。这是首个对围产期诊断的结直肠癌的临床病理、激素和分子特征进行研究的病例系列。我们假设妊娠相关激素因素可能会缓解结直肠癌的晚期表现。 方法 我们对5名在围产期被诊断为结直肠癌的女性进行了回顾性研究，并对她们所患癌症的临床和分子特征进行了研究。 结果 所有患者在确诊时均为IV期结直肠癌；3例原发肿瘤位于直肠，2例位于乙状结肠。肝脏是最常见的转移部位（5名女性中有3名）。免疫组化染色显示雌激素受体α（ERα）和β（ERβ）均为阴性，1例肿瘤显示孕激素受体（PR）低水平阳性（1%）。对每个病例的福尔马林固定石蜡包埋（FFPE）活检组织进行新一代测序，发现所有肿瘤的错配修复（MMR）功能正常，3例存在KRAS突变。种系检测未显示出结直肠癌的遗传易感性；然而，发现了几个意义未明的体细胞变异（VUS）。 讨论 由于诊断困难，围产期的结直肠癌是出现晚期疾病的重要危险因素。虽然我们的研究没有证据表明妊娠期间结直肠癌的发病机制是由妊娠期间雌激素和/或孕激素水平升高所驱动，但其他可能的病因因素，包括胎盘生长因子、妊娠的免疫抑制状态以及妊娠期间的其他生理过程，值得未来进一步研究。