[2050] Immunohistochemistry for Novel Markers in Squamous Cell Carcinoma: Glypican-3 Is Expressed across Anatomic Sites, PAX8 Is Limited in Distribution, and p40 Is Extremely Sensitive

Michael P Gailey, Andrew M Bellizzi. University of Iowa Hospitals and Clinics, Iowa City, IA

Background: Immunohistochemistry (IHC) is generally not considered helpful in assigning the site of origin of a squamous cell carcinoma (SCC). TTF-1 and p16 are modestly useful exceptions. In this vein, we were intrigued by a few recent observations: 1. glypican-3 (GPC3), an oncofetal protein often used in hepatocellular carcinoma (HCC) diagnosis, was identified in gene expression profiling of lung tumors and found to be overexpressed in lung SCC; 2. PAX8, a transcription factor critical in thyroid, kidney, and Müllerian tract, was expressed by a few SCC's in large scale IHC studies; 3. p40, an antibody specific for the ΔNp63 isoform, is gaining traction as an SCC marker due to superior specificity in lung. We examined expression of these 3 proteins in SCC's from diverse anatomic sites and in urothelial carcinoma (UC) (histologically similar/often showing squamous differentiation).
Design: IHC for GPC3, PAX8, and p40 was performed on whole sections from 107 SCC and 11 UC. Slides were independently scored (intensity/extent of staining) by 2 pathologists, blinded to site. Granular, cytoplasmic GPC3 staining in ≥5% of tumor cells and any definite PAX8/p40 nuclear staining were considered positive. Discrepancies were resolved over a two-headed microscope.
Results: Overall, GPC3 was seen in 22/118 (19%) tumors (9 of 12 sites), PAX8 was restricted to cervix and bladder, and p40 was seen in all but 1 tumor (minute focus of residual tumor in a treated esophagus). PAX8 and p40 slides were scored with 100% and GPC3 slides with 93% concordance. Site specific results are shown in the Table.

Protein Expression by Anatomic Site
 GPC3 (n, %)PAX8 (n, %)p40 (n, %)
Anus1/10 (10%)0/10 (0%)10/10 (100%)
Bladder (UC)1/11 (9%)2/11 (18%)11/11 (100%)
Cervix3/11 (27%)3/11 (27%)11/11 (100%)
Esophagus2/7 (29%)0/7 (0%)6/7 (86%)
Larynx3/10 (30%)0/10 (0%)10/10 (100%)
Lung6/12 (50%)0/12 (0%)12/12 (100%)
Penis0/10 (0%)0/10 (0%)10/10 (100%)
Skin0/10 (0%)0/10 (0%)10/10 (100%)
Ventral Tongue/Floor of Mouth1/8 (13%)0/8 (0%)8/8 (100%)
Tongue Base/Tonsil1/8 (13%)0/8 (0%)8/8 (100%)
Vagina4/10 (40%)0/10 (0%)10/10 (100%)
Vulva0/11 (0%)0/11 (0%)11/11 (100%)

Conclusions: GPC3 is not specific to lung SCC and, instead, is often expressed across anatomic sites; pathologists are cautioned against over-relying on this marker in making a diagnosis of HCC. PAX8 is limited in distribution and may have a use in assigning site of origin. p40 is extremely sensitive for SCC (and UC); further studies evaluating its specificity at other sites (e.g., GI/GYN tracts) are warranted.
Category: Techniques

Monday, March 4, 2013 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 305, Monday Morning


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