[1858] EGFR Mutation and p53 Overexpression in the AAH-BAC-Small Adenocarcinoma Sequence of the Lung

SB Yoo, HJ Lee, CT Lee, SH Jheon, JH Chung. Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea

Background: A progression model of atypical adenomatous hyperplasia (AAH) to bronchioloalveolar carcinoma (BAC) to invasive adenocarcinoma(ADC) has been proposed. However, the genetic alterations of the AAH-BAC-ADC sequence are not clearly established. We examined the mutation of the epidermal growth factor receptor (EGFR) gene and p53 protein overexpression in the AAH, BAC and small ADC to understand their role in the pulmonary adenocarcinoma pathogenesis.
Design: Twenty AAH, 39 BAC (19 Noguchi type A and 20 type B) and 32 ADC (Noguchi type C) were enrolled in this study. EGFR mutations at exons 18-21 and p53 protein expression were examined by PCR-direct sequencing and immunohistochemistry, respectively.
Results: Mutations of the EGFR gene were noted in 32 (35.2%) lesions, which included 7 (35.0%) of AAH, 13 (33.3%) of BAC and 12 (37.5%) of small ADC. Eighteen (19.8%) of the mutations were detected as exon 19 deletion, 13 (14.3%) as exon 21 point mutation and 1 (1.1%) as exon 18 point mutation. Overexpression of p53 protein was found in 16 (17.6%) lesions, none of AAH, 4 (10.3%) of BAC and 12 (37.5%) of ADC.

Table 1. Comparison of EGFR gene mutation and expression of p53 protein
Histology (no.)EGFR gene mutation negativeEGFR gene mutation positivep valuep53 protein expression negativep53 protein expression positivep value
AAH (20)13 (65.0%)7 (35.0%)20 (100.0%)0 (0.0%)
BAC (39)26 (66.7%)13 (33.3%)35 (89.7%)4 (10.3%)
ADC (32)20 (62.5%)12 (37.5%)20 (62.5%)12 (37.5%)
Total (91)59 (64.8%)32 (35.2%)0.93575 (82.4%)16 (17.6%)0.001

Conclusions: High frequency and similar incidence of EGFR mutation in AAH, BAC, and ADC supports that EGFR gene mutation seemed to be associated with early stages of pulmonary ADC, and BAC with EGFR mutation might progress into invasive adenocarcinoma easier than those without mutation. On the contrary, p53 overexpression was identified in the late step of the AAH-BAC-ADC sequence model. The genetic alterations of the EGFR and p53 might play a role in the different stages of the peripheral pulmonary adenocarcinoma development.
Category: Pulmonary

Monday, March 22, 2010 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 245, Monday Morning


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