Immunoreactivity for DeltaNp63-p40, a Basal-Type Marker, as a Holistic, Single-Shot Diagnostic Adjunct Approach to Morphology for Lung Cancer Subtyping
Giuseppe Pelosi, Giulio Rossi, Alberto Cavazza, Luisella Righi, Ugo Pastorino, Paolo Scanagatta, Natasha Rekhtman, Angelica Sonzogni, Mauro Papotti. National Cancer Institute and University of Milan School of Medicine, Milan, Italy; Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy; Arcispedale Santa Maria Nuova, Reggio Emilia, Italy; University of Turin, Turin, Italy; National Cancer Institute, Milan, Italy; Memorial Sloan-Kettering Cancer Center, New York; European Institute of Oncology, Milan, Italy
Background: DeltaNp63-p40, a basal-type marker corresponding to non-transactivating or truncated isoforms of the p63 gene family of nuclear transcription factors, is a sensitive detector of squamous cell carcinoma (SQC). Little is know, however, about the diagnostic power of p40 as a single-shot adjunct to morphology when used in a daily routine practice-based, consecutive series of lung carcinomas.
Design: Forty-nine consecutive surgical specimens from 27 adenocarcinomas (AD), 11 SQC, 4 sarcomatoid carcinoma (SC), 3 small cell carcinoma (SCLC), 2 adenosquamous carcinomas (ADSQC), 1 basaloid large cell carcinoma (B-LCC) and 1 large cell neuroendocrine carcinoma (LCNEC) were collected from the routine diagnostic activity over a period of two months and then processed comparatively by immunohistochemistry for p40 (polyclonal antibody), p63 (clone 4A4) and thyroid transcription factor-1 (TTF-1, clone 8G7G3/1). A histologic (H) score was obtained for each antibody multiplying the percentage of positive cells by the immunostaining intensity (dichotomized as low to strong according to internal positive controls).
Results: H-scores for p40, p63 and TTF1 were 0.1±0.4, 25.1±56.7 and 143.2±65.6 for AD; 190.4±11.3, 190.4±11.3 and 0 for SQC; 176.5±32.8, 176.5±32.8 and 20.0±34.6 for biphasic tumors containing SQC lineage (1 SC, 2 ADSQC, 1 B-LCC); 0, 20.0±28.3 and 73.3±53.3 for biphasic tumors containing AD lineage (3 SC); and 1.2±2.2, 20.7±23.3 and 190.0±7.1 for SCLC and LCNEC, respectively (p<0.001). While p40 was always negative in tumors showing AD lineage and in neuroendocrine tumors, p63 was positive (>5% tumor cells) in 7/27 AD, 1/3 gland-differentiated SC and 3 SCLC/LCNEC (p=0.0001). In turn, TTF1 was negative in 3/27 AD and all SQC, but variably positive in all tumor categories.
Conclusions: P40 was a terrific, single-shot marker in lung cancer subtyping, unlike p63 and TTF-1, because excluded by definition SQC or ADSQC when negative and modulated finely morphology to address both TTF1-negative (including some AD, SQC, squamous cell-differentiated SC, ADSQC, B-LCC) and TTF-1 positive (including AD, ADSQC, gland-differentiated SC, SCLC, LCNEC) tumor categories. B-LCC confirmed a basal-type phenotype.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 296, Tuesday Morning