A potential role for targeted therapy in a subset of metastasizing adnexal carcinomas
A potential role for targeted therapy in a subset of metastasizing adnexal carcinomas
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DOI：
10.1038/modpathol.2011.48
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发表时间：
2011-07-01
期刊：
影响因子：
7.5
通讯作者：
Hoang, Mai P.
中科院分区：
文献类型：
--
作者：
Dias-Santagata, Dora;Quynh Lam;Hoang, Mai P.
转移性附件癌是罕见的，因此，目前没有统一的治疗指南。选择性靶向促癌途径的化疗药物可以补充传统的治疗方法。我们做了免疫组织化学（表皮生长因子受体（EGFR）、HER 2和CD 117）、EGFR和ERBB 2荧光原位杂交（FISH）和多重SNaPshots（R）基因分型（检测包括BRAF、EGFR、KRAS、PIK 3CA和TP 53在内的15种癌症基因的复发突变）（3例顶浆腺癌、6例小汗腺腺癌、2例汗腺腺癌、2例汗孔癌和1例侵袭性指乳头状腺癌）。区域淋巴结转移最常见，其次是皮肤和肺。随访12例（5个月~ 8年），1例死于广泛转移。尽管EGFR过表达是该队列中的普遍特征，见于7/11（64%）原发性肿瘤和10/14（71%）转移瘤;但在9例检测的原发性肿瘤和12例转移瘤中，EGFR基因扩增的FISH为阴性。1例原发性肿瘤和3例HER 2过表达的转移瘤的FISH显示，1例顶浆腺癌和相应的转移瘤中ERBB 2基因扩增水平较低。CD 117表达仅见于罕见病例。PIK 3CA（2/12，17%）和TP 53（3/12，25%）突变分别在2例（1例汗腺腺癌，1例汗孔癌）和3例（1例小汗腺癌，1例汗腺腺癌和1例侵袭性指乳头状腺癌）病例中检测到。EGFR抑制剂治疗在蛋白过度表达的转移性附件癌中的作用尚不清楚。靶向治疗包括PI 3 K通路抑制剂可能是一种潜在的治疗罕见的附件癌转移病例。Modern Pathology（2011）24，974-982; doi：10.1038/modpathol.2011.48; 2011年3月18日在线发表
Metastasizing adnexal carcinomas are rare; thus, currently there is no uniform treatment guideline. Chemotherapeutic drugs that selectively target cancer-promoting pathways may complement conventional therapeutic approaches. We performed immunohistochemistry (epidermal growth factor receptor (EGFR), HER2, and CD117), EGFR and ERBB2 fluorescence in situ hybridization (FISH), and multiplexed SNaPshots (R) genotyping (testing for recurrent mutations in 15 cancer genes including BRAF, EGFR, KRAS, PIK3CA, and TP53) on primary tumors and corresponding metastases of 14 metastasizing adnexal carcinomas (three apocrine, six eccrine, two hidradenocarcinomas, two porocarcinomas, and one aggressive digital papillary adenocarcinoma). Metastasis to regional lymph node was most common, followed by skin and then lungs. Follow-up was available in 12 patients (5 months to 8 years) with 1 died of widespread metastases. Although EGFR overexpression was a prevalent feature in this cohort, seen in 7/11 (64%) primary tumors and 10/14 (71%) metastases; FISH for EGFR gene amplification was negative in 9 tested primary tumors and 12 metastases. FISH of the one primary tumor and three metastases with 2 + HER2 overexpression revealed a low level of ERBB2 gene amplification in one apocrine carcinoma and corresponding metastasis. CD117 expression was seen only in rare cases. PIK3CA (2/12, 17%) and TP53 (3/12, 25%) mutations were detected in two (one hidradenocarcinoma, one porocarcinoma) and three (one eccrine, one hidradenocarcinoma, and one aggressive digital papillary adenocarcinoma) cases, respectively. The role of EGFR inhibitor therapy in metastasizing adnexal carcinomas with protein overexpression remains unclear. Targeted therapy including PI3K pathway inhibitors might be a potential treatment for rare cases of adnexal carcinomas with metastases. Modern Pathology (2011) 24, 974-982; doi: 10.1038/modpathol.2011.48; published online 18 March 2011