Basal cell (basaloid) carcinoma of the lung: A new morphologic and phenotypic entity with separate prognostic significance

Brambilla, Élisabeth; Moro, D.; Veale, D; Brichon, Pierre-Yves; Stoebner, Pierre‐Emmanuel; Paramelle, B; Brambilla, Christian

doi:10.1016/0046-8177(92)90260-a

Cited by 179 publications

(128 citation statements)

References 28 publications

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“…This subgroup is typically small (usually in the order of 10% of a cohort) and no specific response to therapy had been associated with it. Recently there has been an effort to better define this group of tumors by using molecular and genetic features as well as morphological features 34 and has discriminated two new tumor entities within morphological large cell carcinoma, the neuroendocrine carcinomas 35 and basaloid carcinomas, 36 both of which have a poor prognosis. Both TTF-1/TP63 and the five-antibody test identify an increased fraction of unclassifiable samples when the tumor had been morphologically diagnosed as large cell ( Figure 5) consistent with an undifferentiated phenotype or with molecular features distinct from adenocarcinoma or squamous cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

A novel five-antibody immunohistochemical test for subclassification of lung carcinoma

Ring¹,

Seitz

Beck

et al. 2009

Modern Pathology

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Malignant epithelial lung carcinoma can be subclassified by histology into several tumor types, including adenocarcinoma and squamous cell carcinoma. The need for a uniform method of classifying lung carcinomas is growing as clinical trials reveal treatment and side effect differences associated with histological subtypes. Diagnosis is primarily performed by morphological assessment. However, the increased use of needle biopsy has diminished the amount of tissue available for interpretation. These changes in how lung carcinomas are diagnosed and treated suggest that the development of improved molecular-based classification tools could improve patient management. We used a 551-patient surgical specimen lung carcinoma retrospective cohort from a regional hospital to assess the association of a large number of proteins with histological type by immunohistochemistry. Five of these antibodies, targeting the proteins TRIM29, CEACAM5, SLC7A5, MUC1, and CK5/6, were combined into one test using a weighted algorithm trained to discriminate adenocarcinoma from squamous cell carcinoma. Antibody-based classification on 600 lM tissue array cores with the fiveantibody test was compared to standard histological evaluation on surgical specimens in three independent lung carcinoma cohorts (combined population of 1111 patients). In addition, the five-antibody test was tested against the two-marker panel thyroid transcription factor-1 (TTF-1) and TP63. Both the five-antibody test and TTF-1/TP63 panel had similarly low misclassification rates on the validation cohorts compared to morphological-based diagnosis (4.1 vs 3.5%). However the percentage of patients remaining unclassifiable by TTF-1/TP63 (22%, 95% CI: 20-25%) was twice that of the five-antibody test (11%, 95% CI: 8-13%). The results of this study suggest the five-antibody test may have an immediate function in the clinic for helping pathologists distinguish lung carcinoma histological types. The results also suggest that if validated in prospectively defined clinical trials this classifier might identify candidates for targeted therapy that are overlooked with current diagnostic approaches.

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Section: Discussionmentioning

confidence: 99%

A novel five-antibody immunohistochemical test for subclassification of lung carcinoma

Ring¹,

Seitz

Beck

et al. 2009

Modern Pathology

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“…The study included 19 adenocarcinoma, 16 squamous carcinoma p16 INK4A inactivation in lung cancer S Gazzeri et al according to WHO classi®cation (1981) and eight basaloid carcinoma considered as basal stem cell proliferation according to Brambilla et al (1992).…”

Section: Tissue Samplesmentioning

confidence: 99%

Mechanisms of p16INK4A inactivation in non small-cell lung cancers

Gazzéri¹,

Gouyer²,

et al. 1998

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The cyclin-dependent kinase inhibitor p16 (p16 INK4A / CDKN2/MTS1) is a potent inhibitor of the cyclin Ddependent phosphorylation of the retinoblastoma gene (Rb) product, the inactivation of which induces loss of Rb-dependent G1 arrest through inappropriate phosphorylation of the Rb protein. To analyse the role of p16 INK4A as a tumor suppressor in the genesis of non small cell lung cancers (NSCLC) and correlate loss of p16 INK4A protein expression to genetic or epigenetic mechanisms, we have performed a comprehensive study of p16 status in a series of 43 NSCLC. To this end, we have investigated p16 INK4A protein expression with immunohistochemistry, deletions of the gene by FISH, and determined the methylation status of exon 1a using a PCR-based methylation assay. Finally, possible mutations were studied by SSCP and subsequent sequencing. Twenty one of the 43 (49%) NSCLC studied exhibited an absence of p16 INK4A nuclear staining. Of these, three (14%) had frameshift or missense mutations, seven (33%) displayed methylation of exon1a and 10 (48%) displayed homozygous deletions. In total, 95% of the tumors with p16 INK4A negative staining carried one of these three alternative genetic or epigenetic alterations. Furthermore, a high degree of chromosome 9 polysomy was found (58%) in those tumors with p16 INK4A inactivation. Taken together these results suggest that deregulation of the p16 gene locus is a frequently occurring event in NSCLC through distinct mechanisms including rare point mutations, promotor methylation and frequent homozygous deletions. Furthermore, our data show that immunohistochemistry is a rapid and an accurate technique for screening of p16 INK4A gene inactivation events that result in loss of protein expression.

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“…When a basaloid carcinoma shows squamous differentiation, the designation as basaloid variant of squamous cell carcinoma is appropriate (table 1). The basaloid variant of squamous cell carcinoma and pure basaloid carcinoma share the same dismal prognosis with a median survival time of 20 months [41,44]. Interestingly basaloid carcinoma disclose a higher frequency of p53 mutation and p53 protein aberrant expression, a higher rate of p16…”

Section: Basaloid Carcinomamentioning

confidence: 99%

“…Basaloid carcinoma is now defined as a variant of large cell carcinoma [41,42]. Basaloid carcinoma presents with relatively small cells forming lobular pattern with a high rate of mitosis (15-100?2 mm -2 ), peripheral palisading and comedo-type necrosis ( fig.…”

Section: Basaloid Carcinomamentioning

confidence: 99%

The new World Health Organization classification of lung tumours

Brambilla

Tv³

et al. 2001

European Respiratory Journal

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622

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Tumour classification systems provide the foundation for tumour diagnosis and patient therapy and a critical basis for epidemiological and clinical studies. This updated classification was developed with the aim to adhere to the principles of reproducibility, clinical significance, and simplicity in order to minimize the number of unclassifiable lesions.Major changes in the revised classification as compared to the previous one (WHO 1981 [1]) include the addition of two pre-invasive lesions to squamous dysplasia and carcinoma in situ; atypical adenomatous hyperplasia and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. Another change is the subclassification of adenocarcinoma: the definition of bronchioalveolar carcinoma has been restricted to noninvasive tumours. There has been substantial evolution of concepts in neuroendocrine lung tumour classification. Large cell neuroendocrine carcinoma (LCNEC) is now recognized as a histologically high grade non small cell carcinoma showing histopathological features of neuroendocrine differentiation as well as immunohistochemical neuroendocrine markers. The large cell carcinoma class has been enriched with several variants, including the LCNEC and the basaloid carcinoma, both with a dismal prognosis. Finally, a new class was defined called carcinoma with pleomorphic, sarcomatoid, or sarcomatous elements, which brings together a number of proliferations characterized by a spectrum of epithelial to mesenchymal differentiation.Immunohistochemistry and electron microscopy are invaluable techniques for diagnosis and subclassification, but our intention was to render the classification simple and practical to every surgical laboratory, so that most lung tumours could be classified by light microscopic criteria.

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Basal cell (basaloid) carcinoma of the lung: A new morphologic and phenotypic entity with separate prognostic significance

Cited by 179 publications

References 28 publications

A novel five-antibody immunohistochemical test for subclassification of lung carcinoma

A novel five-antibody immunohistochemical test for subclassification of lung carcinoma

Mechanisms of p16INK4A inactivation in non small-cell lung cancers

The new World Health Organization classification of lung tumours

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