Heterogeneity of Large Cell Carcinoma of the Lung An Immunophenotypic and miRNA-Based Analysis

Unit of Surgical Pathology, Laboratory of Molecular Pathology, S. Chiara Hospital, Largo Medaglie Oro 9, Trento, Italy.
American Journal of Clinical Pathology (Impact Factor: 2.51). 11/2011; 136(5):773-82. DOI: 10.1309/AJCPYY79XAGRAYCJ
Source: PubMed


Large cell carcinomas (LCCs) of the lung are heterogeneous and may be of different cell lineages. We analyzed 56 surgically resected lung tumors classified as LCC on the basis of pure morphologic grounds, using a panel of immunophenotypic markers (adenocarcinoma [ADC]-specific, thyroid transcription factor-1, cytokeratin 7, and napsin A; squamous cell carcinoma [SQCC]-specific, p63, cytokeratin 5, desmocollin 3, and Δnp63) and the quantitative analysis of microRNA-205 (microRNA sample score [mRSS]). Based on immunoprofiles 19 (34%) of the cases were reclassified as ADC and 14 (25%) as SQCC; 23 (41%) of the cases were unclassifiable. Of these 23 cases, 18 were classified as ADC and 5 as SQCC according to the mRSS. Our data show that an extended panel of immunohistochemical markers can reclassify around 60% of LCCs as ADC or SQCC. However, a relevant percentage of LCCs may escape convincing immunohistochemical classification, and mRSS could be used for further typing, but its clinical relevance needs further confirmation.

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    • "Discussion: Massive sequencing of lung cancer is providing relevant profiles of single tumor subtypes with important information for prognostic and predictive purposes [66] [67]. Data on LCC are currently scant, but it is reasonable to expect that many if not all LCC will display a genetic profile (including microRNAs) [68] [69] aligned to either ADC or SQC. The same holds true for known predictive markers of response to specific therapies, as thymidylate synthase in LCC [70]. "
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    ABSTRACT: Large cell carcinoma (LCC) is a merely descriptive term indicating a subtype of lung cancer with no specific features of small-cell lung cancer (SCLC), adenocarcinoma (ADC) or squamous cell carcinoma (SQC). This diagnosis is allowed on surgical specimens only, whereas its counterpart in biopsy/cytology samples is non-small-cell lung carcinoma (NSCLC), not otherwise specified (NOS). Although these two terms do not fulfill the same concept, they can be interchangeable synonyms at the clinical level, reflecting, in different ways, the inability to define a specific subtype. Immunohistochemistry (IHC), next generation sequencing (NGS) analysis and, historically, electron microscopy have been unveiling diverse cell differentiation lineages in LCC, resulting in LCC-favor ADC, LCC-favor SQC and LCC-favor large-cell neuroendocrine carcinoma (LCNEC), the latter hopefully to be included into the neuroendocrine tumor (NET) group in the future. Paradoxically, however, the interpretation issues of LCC/NSCLC-NOS are not diminishing, but even increasing albeight an accurate diagnosis is oncologically required and crucial. Also, rare LCC/NSCLC-NOS cases exhibiting null/unclear phenotype, are difficult to classify, and this terminology could be maintained for the sake of classification (basically these tumors are serendipitous ADC, as also confirmed by the lack of p40). In this review article, seven relevant issues to LCC have been addressed by using a question-answer methodology, with final key points discussing major interpretation issues. In conclusion, most LCC/NSCLC-NOS may be eventually re-classified and addressed by exploiting IHC and/or molecular testing to satisfy the criteria of precision medicine (the right drug, to the right patient, at the right time).
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    Full-text · Article · Nov 2012 · Modern Pathology
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    No preview · Article · Jan 2013
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