Familial Cancer Laboratory, I Floor, Bancroft Centre, Queensland Institute of Medical Research, Herston Road, Herston, Queensland 4006, Australia.
Clin Cancer Res. 2010 Apr 1;16(7):2214-24. doi: 10.1158/1078-0432.CCR-09-3058. Epub 2010 Mar 9.
The recognition of breast cancer as a spectrum tumor in Lynch syndrome remains controversial. The aim of this study was to explore features of breast cancers arising in Lynch syndrome families.
This observational study involved 107 cases of breast cancer identified from the Colorectal Cancer Family Registry (Colon CFR) from 90 families in which (a) both breast and colon cancer co-occurred, (b) families met either modified Amsterdam criteria, or had at least one early-onset (<50 years) colorectal cancer, and (c) breast tissue was available within the biospecimen repository for mismatch repair (MMR) testing. Eligibility criteria for enrollment in the Colon CFR are available online. Breast cancers were reviewed by one pathologist. Tumor sections were stained for MLH1, PMS2, MSH2, and MSH6, and underwent microsatellite instability testing.
Breast cancer arose in 35 mutation carriers, and of these, 18 (51%) showed immunohistochemical absence of MMR protein corresponding to the MMR gene mutation segregating the family. MMR-deficient breast cancers were more likely to be poorly differentiated (P = 0.005) with a high mitotic index (P = 0.002), steroid hormone receptor-negative (estrogen receptor, P = 0.031; progesterone receptor, P = 0.022), and to have peritumoral lymphocytes (P = 0.015), confluent necrosis (P = 0.002), and growth in solid sheets (P < 0.001) similar to their colorectal counterparts. No difference in age of onset was noted between the MMR-deficient and MMR-intact groups.
MMR deficiency was identified in 51% of breast cancers arising in known mutation carriers. Breast cancer therefore may represent a valid tissue option for the detection of MMR deficiency in which spectrum tumors are lacking.
在林奇综合征中，乳腺癌被认为是一种谱肿瘤，这一观点仍存在争议。本研究旨在探讨林奇综合征家族中乳腺癌的特征。
本观察性研究纳入了来自 90 个家族的大肠癌家族登记处（Colon CFR）中的 107 例乳腺癌病例，这些家族中（a）乳腺癌和结肠癌同时发生，（b）家族符合改良的阿姆斯特丹标准，或至少有一个早发（<50 岁）结直肠癌，以及（c）生物标本库中存在用于错配修复（MMR）检测的乳腺组织。参加 Colon CFR 的资格标准可在网上查阅。由一名病理学家对乳腺癌进行了审查。肿瘤切片用 MLH1、PMS2、MSH2 和 MSH6 染色，并进行微卫星不稳定性检测。
在 35 名突变携带者中发生了乳腺癌，其中 18 名（51%）的 MMR 蛋白免疫组化缺失，与家族中分离的 MMR 基因突变相对应。MMR 缺陷型乳腺癌更可能分化不良（P = 0.005），有较高的有丝分裂指数（P = 0.002），甾体激素受体阴性（雌激素受体，P = 0.031；孕激素受体，P = 0.022），并具有肿瘤周围淋巴细胞（P = 0.015）、融合性坏死（P = 0.002）和实性片状生长（P < 0.001），与结直肠癌相似。在 MMR 缺陷和 MMR 完整组之间，发病年龄没有差异。
在已知突变携带者中发生的乳腺癌中，鉴定出 MMR 缺陷 51%。因此，乳腺癌可能是检测 MMR 缺陷的一种有效组织选择，而在这些谱肿瘤中缺乏 MMR 缺陷。
