p40 & thyroid transcription factor-1 immunohistochemistry: A useful panel to characterize non-small cell lung carcinoma-not otherwise specified (NSCLC-NOS) category

Abstract

Background & objectives: Accurate histopathological subtyping of non-small cell lung carcinoma (NSCLC) is essential for targeted therapeutic agents. Immunohistochemistry (IHC) is helpful in identification of different tumour subtypes. In this study two marker approaches, one each for glandular and squamous cell differentiation was applied to maximize the proportion of accurately subtyped NSCLC not otherwise specified (NOS) tumours on small biopsy samples.

Methods: Two hundred and sixty three consecutive lung biopsies of primary lung carcinoma were prospectively studied. These were subtyped first morphologically and then by IHC for p40 and thyroid transcription factor-1 (TTF-1). The diagnosis of NSCLC-NOS before and after addition of IHC was evaluated. Results were correlated and validated with morphologically proven cases and matched surgical specimens.

Results: Based on morphology, only 140 of the 263 (53.2%) cases of NSCLC were characterized, whereas 123 (46.7%) were classified as NSCLC-NOS type. With addition of IHC (p40 and TTF-1), the latter category reduced to 14.4 per cent and a sum of 225 (85.5%) cases were accurately subtyped into squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma. p40 showed 100 per cent sensitivity and specificity for squamous differentiation whereas TTF-1 showed sensitivity of 85.3 per cent and specificity of 98.1 per cent. Ninety per cent correlation of morphologic subtypes was achieved with matched resected specimens.

Interpretation & conclusions: Our results showed that an approach of using only a two-antibody panel (p40 and TTF-1) might help in reduction of diagnostic category of NSCLC-NOS significantly and contribute in saving tissue for future molecular testing.

Fig. 1

(A) Morphologically differentiated squamous cell carcinomas with intercellular bridges and intracellular keratinization (arrow) (H & E, ×400). (B) p40 immunostain shows strong (3+) and diffuse nuclear positivity. (C) A case of squamous cell carcinomas with pseudoglandular pattern and acantholysis (arrow) (H & E, ×400). (D) p40 shows nuclear positivity. Inset shows negative TTF-1 stain.

Fig. 2

(A) Morphologically differentiated adenocarcinomas with lepidic histologic pattern (H & E, ×400). (B) Thyroid transcription factor-1 immunostain shows strong (3+) and diffuse nuclear positivity. (C) Adenosquamous carcinoma with glandular (arrow) and squamous differentiation (arrowhead) (H & E, ×400). (D) p40 and (E) thyroid transcription factor-1 show nuclear positivity in different cell populations of adenosquamous carcinoma.

Fig. 3

(A) NSCLC-not otherwise specified without clear-cut morphologic differentiation (H & E, ×400). (B) p40 shows nuclear positivity in the same case indicating squamous lineage. (C) Another case of NSCLC not otherwise specified on morphology which is arranged in solid islands (H & E, ×400). (D) thyroid transcription factor-1 shows diffuse nuclear positivity suggesting diagnosis of adenocarcinoma.