[1186] Molecular Characterization of Head and Neck Basaloid Squamous Cell Carcinoma (BSCC).

Oleksandr N Kryvenko, Dhananjay A Chitale, Richard J Zarbo. Henry Ford Hospital, Detroit, MI

Background: BSCC was originally described as a rare aggressive subtype of head & neck squamous cell carcinoma (HNSCC). The diagnosis remains controversial due to overlapping histologic findings with poorly differentiated non-keratinizing SCC (NKSCC) and lack of diagnostic reproducibility. We explore distinct molecular pathways which may aid in the diagnostic stratification and prognostic relevance of HNSCC with basaloid features.
Design: The HNSCCs originally diagnosed as BSCC or SCC with basaloid features from 1990-2010 were analyzed. These were reviewed and reclassified using strict criteria: BSCC: solid, lobular, nested growth pattern, small cells with scant cytoplasm, hyperchromatic nuclei with peripheral palisading, foci of central coagulative necrosis, stromal hyalinosis, abrupt keratinization. Otherwise, cases were classified as NKSCC. Tissue microarray were constructed and the following immunohistochemical stains were done: MIB-1, p53, p16, Cyclin D1, BCL-2, EGFR. High risk HPV was detected by chromogenic in-situ hybridization (CISH) using cocktail probe (genotypes-16, 18, 33, 35, 45, 51, 52, 56, 66). Contingency table analysis of correlation between HPV status and expression of proteins was performed using Fisher's exact test.
Results: Total of 30 cases were retrieved (14-BSCC, 16-NKSCC). Results of the CISH & IHC and correlation between p16 and HR-HPV are summarized in table 1 and 2, respectively. There was high MIB-1 proliferation index in all the cases. Bcl-2 protein was upregulated in 97% of cases.

Table 1
 HPV-posP16-posP53-posCYCLIND1-posEGFR-pos
BSCC9/14, 64.3%7/14, 50%9/14, 64.3%8/14, 57.1%11/14, 78.6%
NKSCC5/15, 33.3%10/16, 62.5%14/16, 87.5%4/16, 25%7/16, 43.8%
P-value0.09540.48840.13360.07320.0522




Table 2
 HPV-negHPV-posTotal
p16neg6612
p16pos9817
Total151429



Conclusions: BSCC of HNSCC are frequently positive for HR-HPV and tumors arising in Waldeyer's ring are 100% positive, indicating HPV driven carcinogenesis. Most of these cases did not have p53 dysregulation. In addition, EGFR was significantly upregulated in BSCC. p16 as surrogate marker for HPV underestimates HPV+ status in Waldeyer's ring BSCC. In contrast, NKSCC appear to have different molecular pathway where p16 is frequently positive but with only 47% HPV+ and negative correlation with EGFR expression. Moreover, p53 is positive in over 87% of NKSCC. We conclude that the molecular pathway of HNSCC differs according to site and morphology. Positive predictive value of p16 regarding HPV status appears to be site and morphology specific.
Category: Head & Neck

Tuesday, March 1, 2011 1:00 PM

Poster Session IV # 137, Tuesday Afternoon

 

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