High-grade non-small cell lung carcinoma: a comparative analysis of the phenotypic profile in small biopsies with the corresponding postoperative material

Abstract

The most recent classification of the lung cancer expanded the diagnostic criteria of its histological subtypes and included its immunophenotypic profile. We performed the study to compare the reliability of selected markers in high-grade nonsmall cell lung carcinoma (NSCLC) in the oligobiopsies with the matched postoperative samples. We evaluated expression of p40, p63, TTF1, cytokeratin 5/6, cytokeratin 7, napsin A, desmoglein 3, desmocollin 3 and mucin secretion as detected by mucicarmine staining. The study cohort included 123 cases of poorly-differentiated NSCLC. The tissue oligobiopsy material was available in 38 cases. Tissue microarrays (TMAs) from all postoperative cases were constructed. Comparing the immunophenotype between postsurgical samples and oligobiopsies we found an almost perfect agreement for most of performed IHC reactions. The highest concordance of results was found for desmoglein 3, CK7, and p40, whereas the lowest-for desmocollin 3. Immunoprofile of the oligobiopsies corresponded well to that in the resection specimens. The most useful markers in poorly differentiated ADs are: TTF1 and napsin A, and for non-keratinizing SCCs: p40, p63, CK5/6 and desmoglein 3.

Intraoperative rapid immunohistochemistry with noncontact antibody mixing for undiagnosed pulmonary tumors

“…Although our results demonstrate that intraoperative rapid IHC is a promising method for identifying histological types in lung cancer, there is still room for improvement. TTF‐1 is a homeodomain‐containing nuclear transcription factor and a member of the NKX2 gene family, 18 which has been used as a specific marker of lung adenocarcinomas 19,20 . However, TTF‐1 is also expressed in pulmonary/extrapulmonary neuroendocrine cancers 21,22 .…”

“…TTF‐1 is a homeodomain‐containing nuclear transcription factor and a member of the NKX2 gene family, 18 which has been used as a specific marker of lung adenocarcinomas. 19 , 20 However, TTF‐1 is also expressed in pulmonary/extrapulmonary neuroendocrine cancers. 21 , 22 TTF‐1 positivity is predictive of a poor prognosis and is detected in 80%–97% of SCLCs but also 50%–75% of large cell neuroendocrine carcinomas.…”

Pan-p63 but not ΔNp63 (p40) expression in undifferentiated carcinoma of the pancreas

“…Gene fusions involving TP63 and TP63 amplifications may influence p63 expression patterns [39,58], but TP63 fusions were not reported in DAin high-grade follicular lymphoma the prevalence of pan-p63-positive cells correlated with TAp63 mRNA expression [59] -TAp63 is an unstable isoform [20], so its mRNA and protein expression levels may not be fully concordant [70]; (9) other markers of squamous differentiation (e.g. CK5/6, CK34βE12, desmocollin-3, desmoglein-3, S100A2, S100A7, SOX2, and glypican-3 [35,77,78,80]) were not examined; however, their diagnostic performance seems to be worse than p40 immunostain, due to compromised specificity or sensitivity [35,77,78,80].…”

“…Both pan-p63 and p40 stains seem to have good sensitivity for the detection of squamous differentiation; squamous cell carcinomas are frequently positive with both markers irrespective of tumour grade [35,49,78,79,80,81,82]. Expression of pan-p63 and p40 in squamous cell carcinomas is typically strong and diffuse [35,46,49,51,77,79,80,81,83] although the most differentiated, keratinised areas are p63-negative [82].…”

“…Importantly, up to 19% and up to 23% of squamous cell carcinomas may be pan-p63-negative and p40-negative, respectively [46,49,83]. The pan-p63 reactivity in pulmonary adenocarcinomas may be present in a wide range of tumoural cells (1-90%) [35,77] in up to 65% of cases [35,49,51,77,78,79,80,82,83]. In contrast, adenocarcinomas may show p40 expression only in rare cases (up to 7%) [35,46,78,80,83] and in a small proportion of tumour cells (range 1-5%) [35,83].…”