Value of P63 and CK5/6 in distinguishing squamous cell carcinoma from adenocarcinoma in lung fine‐needle aspiration specimens

Abstract

The current FDA-approved standard of care for nonsmall cell lung cancer is Carboplastin/Taxol/Avastin based upon an impressive survival benefit; however, patients with squamous carcinoma (SQCC) cannot receive Avastin because of a 30% mortality rate due to fatal hemoptysis. In this study we evaluated the role of cytomorphology and immunohistochemistry in differentiating SQCC from adenocarcinoma (ADC) in lung FNA specimens. The case cohort included 53 FNA cases of nonsmall cell lung carcinoma with surgical pathology follow-up. All FNA specimens were reviewed independently by a panel of cytopathologists to differentiate between SQCC and ADC. The cell block material was available in 23 cases (11 ADC and 12 SQCC) to perform immunohistochemical stains for TTF-1, CK7, CK20, P63, and CK5/6. On surgical resection, 35/53 (66%) cases were diagnosed as ADC and 18/53 (34%) as SQCC. The number of cases classified correctly on the basis of cytomorphology was 66% for ADC and 53% for SQCC (combined accuracy 60%). By immunohistochemical staining, 14/23 (61%) cases expressed TTF-1. Nine cases were TTF-1 negative; eight of the TTF-1 negative cases (89%) were SQCC. Twenty-three cases expressed CK7 (87%); one ADC case (4%) showed focal CK20 positivity. Both P63 and CK5/6 expression was seen in 9/12 (75%) SQCC cases; none of the ADC cases showed this dual expression. Cytomorphology alone may not be able to stratify all cases of nonsmall cell lung carcinoma into ADC and SQCC in FNA specimens. The immune-panel of TTF-1, CK7, CK20, P63, and CK5/6 is useful in differentiating SQCC from ADC.

Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens

“…[14][15][16][17][23][24][25] Because of a large number of cases and use of whole- tissue sections in this study, we were able to examine in greater detail the spectrum of possible coexpression profiles of commonly used markers in adenocarcinoma and squamous cell carcinoma, which serves as the basis for a more fine-tuned algorithm. Specifically, we show that the vast majority of specimens can be classified by TTF-1 and p63, with a third marker (CK5/6) being needed in only a small subset of cases.…”

“…Given the recent insights into the clinical and biological significance of non-small cell carcinoma subtypes, several recent studies have analyzed the utility of various combinations of markers for the distinction of adenocarcinoma and squamous cell carcinoma. These studies were performed in small biopsies, [14][15][16] cytology, 17,23 and tissue microarrays, [24][25][26] and the proposed algorithms include between fourand six-marker panels. Although most studies agree on the inclusion of TTF-1 and p63 in the panel, there is no agreement on the role of additional markers.…”

Immunohistochemical subtyping of nonsmall cell lung cancer not otherwise specified in fine‐needle aspiration cytology

“…8,21,22 Such sensitivity values are usually reported from surgical series; therefore, these figures may further decrease in FNAC samples or bronchial biopsies, due to focal TTF1 expression in some cases of ADC. 13 This marker has been largely used in biopsy or cytological series, because the nuclear reactivity is readily apparent even in poorly cellular samples and its specificity is high. 19 In the current study, after the exclusion of the fully concordant phenotype cases, TTF1 was positive in approximately one-third of the remaining cases (irrespective of the other marker reactivities), and all of them were ADC or LCC with glandular marker expression (the category also termed ''nonsquamous histology'' in clinical trials).…”

“…13,23 The widely used 1A4 monoclonal antibody to p63 recognizes all p63 isoforms, whereas p40 polyclonal antibody is specific for non-transactivating isoforms. 24 It could be argued that some p63þ ADC according to panisoform-specific antibodies may express transactivating p63 isoforms, which are not identified by p40 antibody, as indicated by one of the current authors (G. P.) in a preliminary report.…”

“…6 Several recent studies have demonstrated that different panels of IHC markers may be useful to define a specific cell lineage-namely, distinguishing squamous cell carcinoma (SQCC) from adenocarcinoma (ADC)-not only on surgical material, [7][8][9] but also on cytology 10 or biopsy samples. [11][12][13][14] However, a fraction of poorly differentiated or undifferentiated NSCLC still remains. 3 We retrospectively considered a consecutive series of patients with early NSCLC who were candidates for surgery at the time of the diagnosis for whom preoperative FNAC were only available.…”