Andrea D. Chapman

Thyroid transcription factor 1 in pulmonary adenocarcinoma

Aims: To discover whether variations in thyroid transcription factor 1 (TTF-1) staining in different subtypes and patterns of pulmonary adenocarcinoma are related to the putative origin of the tumour. In addition, to confirm the specificity of TTF-1 for pulmonary (as opposed to other sites) adenocarcinoma, to examine the possible prognostic relevance of TTF-1 positivity in lung cancer, and to review this laboratory’s experience of TTF-1 in diagnostic practice. Materials/Methods: In total, 128 primary lung adenocarcinomas, 106 primary non-pulmonary adenocarcinomas, and 37 pulmonary non-adenocarcinoma tumours were studied. In addition, 100 cases where TTF-1 was used in routine surgical pathology practice were investigated. Immunoperoxidase staining was performed on formalin fixed, paraffin wax embedded sections using anti-TTF-1 antibody. Staining was evaluated semiquantitatively using the frequency and intensity of nuclear positivity. Results: None of the 106 non-pulmonary adenocarcinomas expressed TTF-1 and only three of the 37 non-adenocarcinoma lung cancers, all neuroendocrine carcinomas, were positive. Of the pulmonary adenocarcinomas, 75% were strongly positive for TTF-1. Mucinous (two of six) and poorly differentiated adenocarcinomas (four of 10) were less likely to stain. Of the peripheral adenocarcinomas, 33 of 37 were positive, whereas only seven of 14 of those of bronchial origin stained strongly. Atypical adenomatous hyperplasia strongly expressed TTF-1. No “false positives” were encountered in the 100 routine diagnostic cases. Conclusion: Positive TTF-1 staining is useful in the differential diagnosis of pulmonary adenocarcinomas. TTF-1 may be a lineage marker for tumours arising from the peripheral airway or alveolar epithelium and has no prognostic relevance.

Immune cell infiltrates and prognosis in primary carcinoma of the lung

The prognostic significance of immune cell infiltrates in surgically resected human lung cancer was investigated in 710 patients. Lymphoid infiltrates were quantified on both standard H&E stained sections and, in a subset of 95 cases, using immunohistochemistry and antibodies to CD3, CD8, CD57, CD68, CD79a and S100 to identify various immune cell types. Subjective grading (low, moderate, high) of lymphoid cell infiltrates on H&E sections of tumour and measurement, using image analysis, of overall level of tumour infiltration by any of the immunohistochemically labelled specific immune cell types of the stained sections showed no prognostic significance. However, when a distinction between peritumoural and intratumoural infiltration by particular cell types was made, intratumoural infiltration by high levels of CD3+ and S100+ cells was associated with longer post-operative survival (P = 0.02 and P = 0.045, respectively). In lung cancer, subjective assessment of tumour lymphoid infiltration and overall levels of infiltration by particular immune cell types carries no prognostic significance. Intratumoural infiltration by relatively high numbers of CD3+ T-lymphocytes and Langerhans cells (S100+) is associated with a better patient outcome.