Departments of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Am J Pathol. 2010 Oct;177(4):1611-7. doi: 10.2353/ajpath.2010.100212. Epub 2010 Aug 27.
Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous borderline tumor-serous carcinoma sequence. In this study, we found that advanced-stage, low-grade ovarian serous carcinomas both with and without adjacent serous borderline tumor shared similar regions of loss of heterozygosity. We then analyzed 91 ovarian tumor samples for mutations in TP53, BRAF, and KRAS. TP53 mutations were not detected in any serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas (n = 18). BRAF (n = 9) or KRAS (n = 5) mutation was detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2 stage II, and 2 stage I), only one (2%) had a BRAF mutation and eight (19%) had a KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade serous carcinomas, which contrasts with previous findings, suggests that aggressive, low-grade serous carcinomas are more likely derived from serous borderline tumors without BRAF mutation. In addition, advanced-stage, low-grade carcinoma patients with BRAF or KRAS mutation have a better apparent clinical outcome. However, further investigation is needed.
低级别卵巢浆液性癌被认为是通过腺瘤-浆液性交界性肿瘤-浆液性癌序列发生的。在这项研究中，我们发现，晚期低级别卵巢浆液性癌，无论是否伴有相邻的浆液性交界性肿瘤，都具有相似的杂合性缺失区域。然后，我们分析了 91 个卵巢肿瘤样本中 TP53、BRAF 和 KRAS 的突变情况。TP53 突变在任何浆液性交界性肿瘤（n = 30）或低级别浆液性癌（n = 43）中均未检测到，但在 73%的高级别浆液性癌（n = 18）中检测到。BRAF（n = 9）或 KRAS（n = 5）突变在 47%的浆液性交界性肿瘤中检测到，但在低级别浆液性癌（39 期 III 期，2 期 II 期，2 期 I 期）中，只有 1 例（2%）有 BRAF 突变，8 例（19%）有 KRAS 突变。晚期低级别浆液性癌中 BRAF 突变的低频率与先前的发现相反，这表明侵袭性低级别浆液性癌更可能来源于没有 BRAF 突变的浆液性交界性肿瘤。此外，具有 BRAF 或 KRAS 突变的晚期低级别癌患者具有更好的临床预后。然而，还需要进一步的研究。
