title: A potential role for targeted therapy in a subset of metastasizing adnexal carcinomas.
abstract: 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 SNaPshot® 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.
authors.affiliation: Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Dora
authors.initials: D
authors.lastname: Dias-Santagata
authors.forename: Quynh
authors.initials: Q
authors.lastname: Lam
authors.forename: Kristin
authors.initials: K
authors.lastname: Bergethon
authors.forename: Gabrielle M
authors.initials: GM
authors.lastname: Baker
authors.forename: A John
authors.initials: AJ
authors.lastname: Iafrate
authors.forename: Dinesh
authors.initials: D
authors.lastname: Rakheja
authors.forename: Mai P
authors.initials: MP
authors.lastname: Hoang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D013544:Sweat Gland Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D019869:Phosphatidylinositol 3-Kinases; D011518:Proto-Oncogene Proteins; D048493:Proto-Oncogene Proteins B-raf; D019009:Proto-Oncogene Proteins c-kit; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; D018631:ras Proteins; C117307:KRAS protein, human; C484760:PIK3CA protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C482119:BRAF protein, human