Kanno Kosuke, Nakayama Kentaro, Razia Sultana, Islam Sohel Hasibul, Farzana Zahan Umme, Sonia Shahataj Begum, Sasamori Hiroki, Yamashita Hitomi, Ishibashi Tomoka, Ishikawa Masako, Imamura Kayo, Ishikawa Noriyoshi, Kyo Satoru
Department of Obstetrics and Gynecology, Shimane University Faculty of Medicine, Izumo 693-8501, Japan.
Department of Obstetrics and Gynecology, Nagoya City University East Medical Center, Nagoya 464-8547, Japan.
Curr Issues Mol Biol. 2024 Aug 25;46(9):9376-9385. doi: 10.3390/cimb46090555.
Ovarian cancer is classified as type 1 or 2, representing low- and high-grade serous carcinoma (LGSC and HGSC), respectively. LGSC arises from serous borderline tumor (SBT) in a stepwise manner, while HGSC develops from serous tubal intraepithelial carcinoma (STIC). Rarely, HGSC develops from SBT and LGSC. Herein, we describe the case of a patient with HGSC who presented with SBT and LGSC, and in whom we analyzed the molecular mechanisms of carcinogenesis. We performed primary debulking surgery, resulting in a suboptimal simple total hysterectomy and bilateral salpingo-oophorectomy due to strong adhesions. The diagnosis was stage IIIC HGSC, pT3bcN0cM0, but the tumor contained SBT and LGSC lesions. After surgery, TC (Paclitaxel + Carbopratin) + bevacizumab therapy was administered as adjuvant chemotherapy followed by bevacizumab as maintenance therapy. The tumor was chemo-resistant and caused ileus, and bevacizumab therapy was conducted only twice. Next-Generation Sequencing revealed (p.G12V) and (p.W184*) mutations in all lesions. Interestingly, the TP53 mutation was not detected in every lesion, and immunohistochemistry showed those lesions with wild-type p53. was amplified in the HGSC lesions. DNA methylation analysis did not show differentially methylated regions. This case suggests that SBT and LGSC may transform into HGSC via p53 dysfunction due to amplification.
卵巢癌分为1型或2型，分别代表低级别和高级别浆液性癌（LGSC和HGSC）。LGSC以逐步的方式起源于浆液性交界性肿瘤（SBT），而HGSC则起源于输卵管浆液性上皮内癌（STIC）。极少情况下，HGSC由SBT和LGSC发展而来。在此，我们描述了1例表现为SBT和LGSC的HGSC患者的病例，并分析了其致癌的分子机制。我们进行了初次肿瘤细胞减灭术，由于粘连严重，最终进行了次优的单纯全子宫切除术和双侧输卵管卵巢切除术。诊断为IIIC期HGSC，pT3bcN0cM0，但肿瘤包含SBT和LGSC病灶。术后，给予TC（紫杉醇+卡铂）+贝伐单抗作为辅助化疗，随后给予贝伐单抗作为维持治疗。肿瘤具有化疗耐药性并导致肠梗阻，贝伐单抗仅进行了2次治疗。二代测序显示所有病灶均存在（p.G12V）和（p.W184*）突变。有趣的是，并非每个病灶都检测到TP53突变，免疫组化显示这些病灶为野生型p53。HGSC病灶中检测到 扩增。DNA甲基化分析未显示差异甲基化区域。该病例提示，SBT和LGSC可能由于 扩增导致p53功能障碍而转化为HGSC。
