[515] Comparative Analysis of EGFR Immunohistochemical Expression and Mutational Analysis in Metastatic Basal Cell Carcinomas.

William R Porter, John D Schwartz, Mitual B Amin, LeeAnn Thal, Dmitry Kazakov, Michal Michal, Shakil Merchant, Rajwant K Malhotra. William Beaumont Hospital, Royal Oak, MI; University Hospital Plzen, Pilsen, Czech Republic; Methodist Hospital, San Antonio, TX

Background: Basal cell carcinoma is a common and indolent tumor that rarely metastasizes (incidence: 0.0028 to 0.5%). The median survival of metastatic basal cell carcinoma (MBCC) is 10-14 months and the 5-year survival is approximately 10%. One of our prior studies examined EGFR immunohistochemical expression in MBCC, which showed positive expression in all examined cases. A literature search did not reveal any studies on EGFR mutation analysis in MBCC. Given the poor prognosis and desire of oncologists to try newer targeted therapy as a last resort, such as Imatinib, examination for EGFR mutations in these aggressive tumors could be potentially fruitful.
Design: Seven samples were selected of metastatic disease to the following: kidney(1), lung(2), lymph node(2), soft tissue(1), and vetebra (1). The vetebral metastasis was excluded from mutation analysis due to decalcificied nature of specimen. Tumors were stained for EGFR (DakoCytomation pharmDx kit) as directed. RNA was extracted from corresponding paraffin blocks using the RNAeasy FFPE kit, and DNA was extracted using the QIAamp DNA mini kit. In-house real time PCR was used to identify variant III EGFR. The QIAGEN EGFR PCR kit was used to identify 28 of the most common mutations of the EGFR gene.
Results: There was positive EGFR immunohistochemical expression in all seven cases. No EGFR mutations were detected in the 4 samples that could be analyzed (wild type). Mutation analysis for EGFR variant III showed similar absence of the mutation in 4 samples. Three cases had insufficient tissue for complete mutational analysis.

Mutation Analysis
SampleMetastatic SiteEGFR IHCEGFR vIII mutationEGFR Mutation
1Kidney2+AbsentAbsent
2Lung2+AbsentAbsent
3Lymph Node2+AbsentAbsent
4Lymph Node2+QNSAbsent
5Lung2+AbsentQNS
6Soft tissue3+QNSQNS
7Vetebrae2+n/an/a
IHC: Immunohistochemistry, scored 1-3+; QNS: Quantity not sufficient for analysis


Conclusions: This case series of MBCC did not reveal mutations within EGFR genes. Mutational analysis does not correlate with EGFR IHC expression, and positive IHC expression can be misleading and lead to inappropriate treatment as recent studies have shown that patients with EGFR mutations are the most likely subset to respond to selective anti-EGFR tyrosine kinase inhibitors. Recent studies suggest a new direction, targeting mutations in the hedgehog signaling pathway and associated targeted therapy.
Category: Dermatopathology

Wednesday, March 2, 2011 1:00 PM

Poster Session VI # 112, Wednesday Afternoon

 

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