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) , 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.
|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%)|