PMID- 21423156
OWN - NLM
STAT- MEDLINE
DCOM- 20111025
LR  - 20230210
IS  - 1530-0285 (Electronic)
IS  - 0893-3952 (Linking)
VI  - 24
IP  - 7
DP  - 2011 Jul
TI  - A potential role for targeted therapy in a subset of metastasizing adnexal 
      carcinomas.
PG  - 974-82
LID - 10.1038/modpathol.2011.48 [doi]
AB  - 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(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.
FAU - Dias-Santagata, Dora
AU  - Dias-Santagata D
AD  - Department of Pathology, Massachusetts General Hospital and Harvard Medical 
      School, Boston, MA, USA.
FAU - Lam, Quynh
AU  - Lam Q
FAU - Bergethon, Kristin
AU  - Bergethon K
FAU - Baker, Gabrielle M
AU  - Baker GM
FAU - Iafrate, A John
AU  - Iafrate AJ
FAU - Rakheja, Dinesh
AU  - Rakheja D
FAU - Hoang, Mai P
AU  - Hoang MP
LA  - eng
PT  - Journal Article
DEP - 20110318
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
RN  - 0 (KRAS protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.137 (PIK3CA protein, human)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Carcinoma/*genetics/*metabolism/pathology
MH  - Class I Phosphatidylinositol 3-Kinases
MH  - DNA Mutational Analysis
MH  - Drug Delivery Systems
MH  - ErbB Receptors/analysis/biosynthesis/genetics
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Neoplasm Metastasis/*genetics/pathology
MH  - Phosphatidylinositol 3-Kinases/genetics
MH  - Proto-Oncogene Proteins/genetics
MH  - Proto-Oncogene Proteins B-raf/genetics
MH  - Proto-Oncogene Proteins c-kit/analysis/biosynthesis/genetics
MH  - Proto-Oncogene Proteins p21(ras)
MH  - Receptor, ErbB-2/analysis/biosynthesis/genetics
MH  - Sweat Gland Neoplasms/*genetics/*metabolism/pathology
MH  - Tumor Suppressor Protein p53/genetics
MH  - ras Proteins/genetics
EDAT- 2011/03/23 06:00
MHDA- 2011/10/26 06:00
CRDT- 2011/03/23 06:00
PHST- 2011/03/23 06:00 [entrez]
PHST- 2011/03/23 06:00 [pubmed]
PHST- 2011/10/26 06:00 [medline]
AID - S0893-3952(22)02848-4 [pii]
AID - 10.1038/modpathol.2011.48 [doi]
PST - ppublish
SO  - Mod Pathol. 2011 Jul;24(7):974-82. doi: 10.1038/modpathol.2011.48. Epub 2011 Mar 
      18.