Department of Pathology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Int J Gynecol Pathol. 2011 Jan;30(1):22-9. doi: 10.1097/PGP.0b013e3181ed89b3.
According to a tumor progression model, low-grade ovarian serous carcinomas may evolve from serous borderline tumors or micropapillary tumors. We sought to investigate the role of and associations between BRAF mutational status, extracellular signal regulated kinase activation, and p16(INK4A) expression in various types of ovarian serous tumors. We analyzed 29 typical ovarian serous borderline tumors, 8 micropapillary tumors, 4 low-grade invasive ovarian serous carcinomas, and 24 high-grade invasive ovarian serous carcinomas for the BRAF mutational status at codon 600; in addition, expression levels of the downstream signaling protein extracellular signal regulated kinase and the p16(INK4A) tumor suppressor protein were assessed by immunohistochemistry. There was a decline in p16(INK4A) expression from serous borderline tumors to micropapillary tumors with almost complete loss in low-grade invasive carcinomas. High-grade carcinomas had a variable p16(INK4A) expression pattern. We found a T1799A BRAF mutation in 12 typical serous borderline tumors (41%) and 1 micropapillary tumor (12.5%). No mutations were found in the low-grade and high-grade invasive carcinomas (0%). Among the typical borderline tumors, cases with BRAF mutations tended to have stronger p16(INK4A) expression compared with cases with wild-type BRAF. No other correlations were identified between the BRAF mutational status and expression levels of the analyzed proteins. Loss of p16(INK4A) expression may be a pathogenetic factor in the progression from serous borderline tumors to low-grade invasive carcinomas. The divergent molecular profiles support the theory that high-grade carcinomas are unrelated to serous borderline tumors or low-grade carcinomas.
根据肿瘤进展模型，低级别卵巢浆液性癌可能起源于浆液性交界性肿瘤或微乳头肿瘤。我们旨在研究 BRAF 突变状态、细胞外信号调节激酶激活与各种卵巢浆液性肿瘤中 p16(INK4A)表达之间的关系和相关性。我们分析了 29 例典型的卵巢浆液性交界性肿瘤、8 例微乳头肿瘤、4 例低级别浸润性卵巢浆液性癌和 24 例高级别浸润性卵巢浆液性癌的 BRAF 第 600 密码子突变状态；此外，还通过免疫组织化学评估了下游信号蛋白细胞外信号调节激酶和 p16(INK4A)肿瘤抑制蛋白的表达水平。p16(INK4A)表达从浆液性交界性肿瘤到微乳头肿瘤逐渐下降，低级别浸润性癌几乎完全缺失。高级别癌的 p16(INK4A)表达模式存在差异。我们在 12 例典型浆液性交界性肿瘤（41%）和 1 例微乳头肿瘤（12.5%）中发现 T1799A BRAF 突变。低级别和高级别浸润性癌未发现突变（0%）。在典型的交界性肿瘤中，BRAF 突变病例的 p16(INK4A)表达倾向于比 BRAF 野生型病例更强。在 BRAF 突变状态与分析蛋白的表达水平之间未发现其他相关性。p16(INK4A)表达缺失可能是从浆液性交界性肿瘤到低级别浸润性癌进展的发病因素。不同的分子谱支持高级别癌与浆液性交界性肿瘤或低级别癌无关的理论。
