乳腺癌分子类型的蛋白表达谱和流行模式——基于沙特人群的研究。
Protein expression profile and prevalence pattern of the molecular classes of breast cancer--a Saudi population based study.
机构信息
Pathology Department, College of Medicine, University of Dammam, Dammam, Saudi Arabia.
出版信息
BMC Cancer. 2010 May 21;10:223. doi: 10.1186/1471-2407-10-223.
BACKGROUND
Breast cancer is not a single entity but a diverse group of entities. Advances in gene expression profiling and immunohistochemistry as its surrogate marker have led to the unmasking of new breast cancer molecular subtypes, resulting in the emergence of more elaborate classification systems that are therapeutically and prognostically more predictive. Molecular class distribution across various ethnic groups may also reveal variations that can lead to different clinical outcomes in different populations.
METHODS
We aimed to analyze the spectrum of molecular subtypes present in the Saudi population. ER, PR, HER2, EGFR and CK5/6 were used as surrogate markers for gene expression profiling to classify 231 breast cancer specimens. Correlation of each molecular class with Ki-67 proliferation index, p53 mutation status, histologic type and grade of the tumor was also carried out.
RESULTS
Out of 231 cases 9 (3.9%) were classified as luminal A (strong ER +ve, PR +ve or -ve), 37 (16%) as luminal B (weak to moderate ER +ve, and/or PR +ve), 40 (17.3%) as HER2+ (strong or moderately positive HER 2 with confirmation by silver enhanced in-situ hybridization) and 23 (10%) as basal (CK5/6 or EGFR +ve). Co-positivity of different markers in varied patterns was seen in 23 (10%) of cases which were grouped into a hybrid category comprising luminal B-HER2, HER2-basal and luminal-basal hybrids. Ninety nine (42.8%) of the tumors were negative for all five immunohistochemical markers and were labelled as unclassified (penta negative). A high Ki-67 proliferation index was seen in basal (p=0.007) followed by HER2+ class. Overexpression of p53 was predominantly seen in HER2+(p=0.001) followed by the basal group of tumors. A strong correlation was noted between invasive lobular carcinoma and hormone receptor expression with 8 out of 9 lobular carcinoma cases (88.9%) classifiable as luminal cancers. Otherwise, there was no association between the molecular class and the histologic type or grade of the tumor.
CONCLUSIONS
Subtyping by use of this immunohistochemical panel revealed a prevalence pattern that is unique to our population; luminal tumors comprised only 19.9%, and the unclassified group (penta negative) 42.8%, a distribution which is distinctive to our population and in contrast with all Western studies. The presence of a predominant unclassified group also suggests that the currently used molecular analytic spectrum may not completely encompass all molecular classes and there is a need to further refine and develop the existing classification systems.
背景
乳腺癌不是单一实体，而是多种实体的集合。基因表达谱分析和免疫组织化学作为其替代标志物的进展，揭示了新的乳腺癌分子亚型，导致出现了更精细的分类系统，这些系统在治疗和预后方面更具预测性。不同种族群体的分子分类分布也可能揭示出不同的变异，从而导致不同人群的临床结果不同。
方法
我们旨在分析沙特人群中存在的分子亚型谱。使用 ER、PR、HER2、EGFR 和 CK5/6 作为基因表达谱分析的替代标志物，对 231 例乳腺癌标本进行分类。还对每个分子类别与 Ki-67 增殖指数、p53 突变状态、肿瘤的组织学类型和分级进行了相关性分析。
结果
在 231 例病例中，有 9 例（3.9%）被归类为 luminal A（强 ER +ve、PR +ve 或 -ve），37 例（16%）为 luminal B（弱至中度 ER +ve，和/或 PR +ve），40 例（17.3%）为 HER2+（强或中度阳性 HER 2，通过银增强原位杂交证实），23 例（10%）为基底（CK5/6 或 EGFR +ve）。不同标记物的共阳性以不同的模式出现在 23 例（10%）病例中，这些病例被归入包含 luminal B-HER2、HER2-基底和 luminal-basal 杂交的混合类别。99 例（42.8%）肿瘤对所有 5 种免疫组织化学标志物均为阴性，被标记为未分类（五阴性）。基底组的 Ki-67 增殖指数较高（p=0.007），其次是 HER2+组。p53 过表达主要见于 HER2+（p=0.001），其次是基底组肿瘤。浸润性小叶癌与激素受体表达之间存在很强的相关性，9 例小叶癌中有 8 例（88.9%）可归类为 luminal 癌。否则，分子类型与肿瘤的组织学类型或分级之间没有关联。
结论
使用这种免疫组织化学面板进行亚分型揭示了一种独特于我们人群的流行模式；luminal 肿瘤仅占 19.9%，未分类组（五阴性）占 42.8%，这种分布与我们人群的分布不同，与所有西方研究也不同。大量的未分类组也表明，目前使用的分子分析谱可能无法完全包含所有的分子类型，因此需要进一步细化和发展现有的分类系统。
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