IMP3: An Immunohistochemical Marker for Invasive Squamous Cell Carcinoma and Its High-Grade Precursor Lesions of the Lung
JJ Findeis-Hosey, Q Yang, LA McMahon, BO Spaulding, F Li, H Xu. University of Rochester Medical Center, Rochester, NY; Dako North America, Carpinteria, CA
Background: Insulin-like growth factor-II messenger RNA-binding protein-3 (IMP3) has been reported to be expressed in multiple malignant neoplasms, but with only limited studies in squamous cell carcinoma (SCC) of the lung and none examining IMP3 expression in squamous precursor lesions. The aim of this study was to examine IMP3 expression in squamous precursor lesions including basal cell hyperplasia (BCH), squamous metaplasia (SM), low grade dysplasia (LGD), high grade dysplasia (HGD), and squamous cell carcinoma in situ (CIS).
Design: A total of 97 resected lung SCCs were examined for squamous precursor lesions including BCH, SM, LGD, HGD and/or CIS. Thirteen cases with such changes were identified on H&E-stained sections. Sections with these precursor lesions and tissue microarrays constructed from 97 invasive SCC cases were immunohistochemically studied using a monoclonal antibody against IMP3 (Dako). Cytoplasmic staining was considered positive. The percentage of positively stained cells was recorded and the staining intensity was graded as negative, weak, moderate or strong. A p value of <0.05, as determined by two-tailed Fisher exact test was considered statistically significant.
Results: Eighty-six (88.7%) of 97 SCCs were IMP3 positive with predominantly strong and diffuse staining. In 13 cases with precursor lesions, there were 1 BCH, 2 SM, 3 LGD, 9 HGD and 10 CIS. All 9 cases with HGD had positive IMP3 staining in the HGD area, with moderate to strong staining in 7 (77.8%) of 9 cases. All 10 cases with CIS had positive IMP3 staining in the CIS area, with moderate to strong staining in 8 (80.0%) of 10 cases. In 1 (33.3%) of 3 cases with LGD there was weak staining in <5% of cells. There was no IMP3 staining in normal bronchial epithelium, BCH or SM. The difference in IMP3 staining between low risk precursor lesions (BCH, SM and LGD) and high risk precursor lesions (HGD and CIS) was statistically significant (p<0.01).
Conclusions: IMP3 is expressed in a majority of cases of HGD, CIS and invasive SCC of the lung. These findings indicate that IMP3 may play an important role in the initiation and progression of pulmonary SCC. Additionally, IMP3 may have utility in small biopsy or fine needle aspiration specimens to highlight HGD and CIS. The identification of these cells is critical as patients with such lesions are at a higher risk of developing invasive SCC.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 240, Wednesday Morning