[1770] Expression of Squamous Markers in Lung Adenocarcinoma (AD): Clinicopathologic and Molecular Correlates, and Implications for Differentiation from Squamous Cell Carcinoma (SqCC)

DC Ang, H Ghaffar, MF Zakowski, J Teruya-Feldstein, AL Moreira, N Rekhtman. Memorial Sloan-Kettering Cancer Center, New York, NY

Background: The distinction of lung AD from SqCC has gained increased importance due to recent emergence of histology-based therapies. Immunohistochemistry (IHC) for squamous markers (p63 and high-molecular weight keratins [HMWCK]) in combination with TTF-1 has been suggested to aid in this classification. However, the precise rate, coexpression profiles, clinicopathologic and molecular correlates for these markers in AD have not been established.
Design: IHC for p63 (4A4), HMWCK (34βE12), and TTF-1 was performed on 185 unselected AD, including 88 consecutive resections and 97 tumors represented in tissue microarrays. Reactivity was scored as positive (POS) [>20%], focal (FOC) [<20%], or negative (NEG) [0], and correlated with various clinicopathologic parameters and mutations in EGFR and KRAS.
Results: Of 185 AD, p63 was POS or FOC in 6% and 23%, and 34βE12 in 29% and 21%, respectively. While p63 was only rarely diffuse [>50% tumor cells] (n=3, 1.6%), AD with diffuse 34βe12 were common (n=39, 21%). p63 was strongly associated with TTF-1 coexpression: POS or FOC p63 was seen in 31% of TTF-1 POS AD vs only FOC p63 was seen in 9% of TTF-1 NEG AD (P=0.041). In contrast, 34βE12 was equally distributed in TTF-1 POS and NEG tumors. There was no association of p63 or 34βE12 with histologic patterns of AD, but there was a trend for p63 in bronchioloalveolar-predominant tumors. Neither p63 nor 34βE12 were associated with age, gender, smoking, stage, survival, and EGFR or KRAS mutations.

Coexpression profiles of squamous markers and TTF-1 in lung AD (n=185).

	TTF-1 POS or FOC n=163 (88%)			TTF-1 NEGTIVE n=22 (12%)
	34βE12 POS	34βE12 FOC	34βE12 NEG	34βE12 POS	34βE12 FOC	34βE12 NEG
p63 POS	6 (3%)	1 (0.5%)	4 (2%)	0 (0)	0 (0)	0 (0)
p63 FOC	16 (9%)	9 (5%)	14 (8%)	1 (0.5%)	1 (0.5%)	0 (0)
p63 NEG	23 (12%)	22 (12%)	68 (37%)	7 (4%)	6 (3%)	7 (4%)

Conclusions: Reactivity for both p63 and 34βE12 is frequent in lung AD, therefore neither p63 nor 34βE12 alone can be used to distinguish AD from SqCC. However, no AD in this study had a 3-marker coexpression profile that overlapped with typical SqCC (TTF-1 NEG/p63 POS/34βE12 POS), suggesting the utility of a panel approach. Further studies are needed to elucidate the significance of p63 restriction to TTF-1 POS AD, and to determine whether there is a biological or clinical significance of squamous marker expression in lung AD.
Category: Pulmonary

Wednesday, March 24, 2010 9:30 AM

Poster Session V # 242, Wednesday Morning