[399] Desmoglein-3 Is Inferior to Cytokeratin 5 and p63 in the Cytologic Diagnosis of Squamous Cell Carcinoma (SQC) of the Lung.

Scott R Lauer, Momin T Siddiqui, Cynthia Cohen, Michelle D Reid. Emory University Hospital, Atlanta, GA

Background: Current treatment strategies for lung carcinoma are dependent on the accurate histologic and cytologic classification of these tumors. Several immunohistochemical (IHC) stains have emerged as frontrunners in their diagnosis and subtyping. One such IHC stain is desmoglein-3 (DSG-3), a calcium-binding transmembrane glycoprotein component of desmosomes in vertebrate epithelial cells. It has recently been shown to have a high sensitivity and specificity for the diagnosis (Dx) of lung SQC. We examined DSG-3 in 43 histologically proven lung carcinomas and compared its performance to that of cytokeratin 5 (CK5) and p63, well-known markers of SQC.
Design: A total of 43 resected/biopsied histologically confirmed lung adenocarcinomas (AD) (25), SQC (13) and poorly differentiated carcinomas (PDC) (5) with previous FNA and adequate cell blocks were selected for IHC staining with SQC markers DSG-3, CK5 and p63. Staining was graded as (0), negative; focal, <30% of cells with cytoplasmic staining; and diffuse, ≥ 30% of cells staining. Based on IHC findings a cytologic Dx was rendered and compared to the gold standard histologic Dx.
Results: The results are summarized in Table 1.

Results of IHC Staining with DSG-3, CK5 and P63

Stain	DSG-3	CK5	p63	CK5 & p63
Dx	+	+	+	+
AD (n=25)	1 (4%)	4 (16%)	6 (24%)	0 (0%)
SQC (n=13)	6 (46%)	12 (92%)	10 (77%)	10 (77%)
PDC (n=5)	1 (20%)	1 (20%)	1 (20%)	1 (20%)
Total (n=43)	8 (19%)	7 (16%)	17 (33%)	11 (26%)

All histologically proven SQC's were confirmed as such on IHC. DSG-3 was focally positive in one lung AD and in 46% of lung SQC. When positive in SQC, staining was always focal, weak and difficult to interpret unlike CK5 and p63, which were diffusely and strongly positive. CK5 and p63 were both positive in 77% of lung SQCs. CK5 and p63 were never both positive in AD. Of the 43 tumors, a single PDC was the only tumor that was strongly and diffusely DSG-3 positive. This tumor was also strongly positive for CK5 and p63, confirming a cytologic diagnosis of SQC.
Conclusions: DSG-3 is a less sensitive IHC marker of squamous differentiation than CK5 and p63. The latter both stain SQC strongly and diffusely; DSG-3 is a weak and patchy cytoplasmic stain and is sometimes difficult to interpret. Because of its negativity in the majority of AD it may have limited usefulness in the cytologic distinction between SQC and AD. Compared to CK5 and p63, DSG-3 is a far less definitive marker of squamous differentiation and is not recommended for routine tumor diagnostics, unless sensitivity improves.
Category: Cytopathology

Tuesday, March 1, 2011 9:30 AM

Poster Session III # 83, Tuesday Morning