Departments of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
Int J Gynecol Pathol. 2012 Jul;31(4):297-303. doi: 10.1097/PGP.0b013e31823f8482.
Nongastrointestinal-type mucinous borderline tumors have been described as displaying endocervical and serous differentiation and hence have been termed "endocervical-type" mucinous borderline tumors, "mixed-epithelial papillary cystadenoma of borderline malignancy of mullerian type," or "atypical proliferative seromucinous tumors." A striking feature of these tumors is their frequent association with endometriosis, which has been reported in a third to a half of cases. This is an unusual finding, as pure endocervical and serous tumors are not usually associated with endometriosis. ARID1A is a recently identified tumor suppressor, which frequently loses its expression and is mutated in endometrium-related carcinomas including ovarian clear cell, ovarian endometrioid, and uterine endometrioid carcinomas. Although ARID1A mutations and their expression have been studied in gynecologic cancer, the expression pattern of ARID1A has not been investigated in ovarian atypical proliferative (borderline) tumors. In this study, we analyzed ARID1A expression in serous, gastrointestinal-type and endocervical-type (seromucinous) mucinous, and endometrioid atypical proliferative (borderline) tumors using immunohistochemistry and performed mutational analysis in selected cases. We observed loss of ARID1A staining in 8 (33%) of 24 seromucinous tumors. In contrast, ARID1A staining was retained in all the other 32 tumors except in 1 endometrioid tumor (P<0.01). Mutational analysis was performed on 2 representative seromucinous tumors, which showed complete loss of ARID1A. Both tumors harbored somatic inactivating ARID1A mutations. Previous studies have reported loss of expression and/or mutation of ARID1A in 30% to 57% of endometrioid and clear cell carcinomas but only rarely in serous tumors. In summary, these tumors often contain endocervical-type mucinous epithelium, but they typically display papillary architecture, unlike most endocervical neoplasms, and their immunophenotype is different from both endocervical and serous tumors. Moreover, they frequently contain ciliated cells, endometrial-type cells, cells with abundant eosinophilic cytoplasm, and hobnail-shaped cells, all of which can be found in endometrioid tumors. The loss of expression of ARID1A and the presence of inactivating mutations of the ARID1A gene further link this tumor to endometrioid and clear cell tumors, as does the frequent association with endometriosis. Accordingly, we suggest designating these tumors "atypical proliferative (borderline) papillary müllerian tumors" as this designation more accurately reflects their clinicopathologic, immunohistochemical, and molecular genetic features.
非胃肠道型黏液性交界性肿瘤被描述为显示宫颈内膜和浆液分化，因此被称为“宫颈内膜型”黏液性交界性肿瘤、“混合上皮乳头状交界性黏液性囊腺瘤，苗勒型”或“非典型增生性分泌性黏液瘤”。这些肿瘤的一个显著特征是它们经常与子宫内膜异位症有关，据报道，有三分之一到一半的病例存在子宫内膜异位症。这是一个不寻常的发现，因为纯宫颈内膜和浆液性肿瘤通常与子宫内膜异位症无关。ARID1A 是最近发现的一种肿瘤抑制因子，在包括卵巢透明细胞癌、卵巢子宫内膜样癌和子宫子宫内膜样癌在内的与子宫内膜相关的癌中，其表达经常缺失并发生突变。尽管 ARID1A 突变及其表达已在妇科癌症中进行了研究，但 ARID1A 的表达模式尚未在卵巢非典型增生（交界性）肿瘤中进行研究。在这项研究中，我们使用免疫组织化学分析了浆液性、胃肠道型和宫颈内膜型（黏液性浆液性）、子宫内膜样非典型增生（交界性）肿瘤中 ARID1A 的表达，并在选定的病例中进行了突变分析。我们观察到 24 例黏液性浆液性肿瘤中有 8 例（33%）存在 ARID1A 染色丢失。相比之下，除了 1 例子宫内膜样肿瘤外，所有其他 32 例肿瘤均保留了 ARID1A 染色（P<0.01）。对 2 例具有代表性的黏液性浆液性肿瘤进行了突变分析，这 2 例肿瘤完全丧失了 ARID1A。这两个肿瘤均存在体细胞失活的 ARID1A 突变。以前的研究报告称，在 30%至 57%的子宫内膜样癌和透明细胞癌中存在 ARID1A 的表达缺失和/或突变，但在浆液性肿瘤中很少见。总之，这些肿瘤通常含有宫颈内膜型黏液上皮，但它们通常表现为乳头状结构，与大多数宫颈内瘤变不同，其免疫表型与宫颈内膜和浆液性肿瘤均不同。此外，它们经常含有纤毛细胞、子宫内膜样细胞、富含嗜酸性细胞质的细胞和钉突状细胞，所有这些细胞都可以在子宫内膜样肿瘤中找到。ARID1A 表达的缺失和 ARID1A 基因的失活突变的存在进一步将这种肿瘤与子宫内膜样癌和透明细胞癌联系起来，与子宫内膜异位症的频繁发生也是如此。因此，我们建议将这些肿瘤命名为“非典型增生（交界性）乳头状苗勒型肿瘤”，因为这种命名更准确地反映了它们的临床病理、免疫组织化学和分子遗传学特征。
