Dataset Information

Neuroendocrine differentiation distinguishes basaloid variant of lung squamous cell carcinoma.

ABSTRACT:

Background

Neuroendocrine (NE) differentiation is widely studied in non-small cell lung carcinomas (NSCLC) however, its significance remains unclear in basaloid squamous cell carcinomas (B-SqCC). This study aims to assess the extent of NE differentiation in B-SqCC and characterize the underlying molecular process.

Methods

This study evaluated resected B-SqCC, small cell lung cancer (SCLC) and poorly differentiated SqCC (PD-SqCC) from 2005 to 2020 at the Ottawa Hospital. Samples were subject to pathological review, immunohistochemistry (IHC) and survival analysis. Gene expression analysis was performed on B-SqCC samples exhibiting NE+ and NE- regions (paired samples) to identify differentially expressed genes (DEGs). These DEGs were subsequently validated in unpaired B-SqCC and TCGA samples.

Results

B-SqCC cases were more likely to exhibit nuclear molding, resetting and peripheral palisading than PD-SqCC. B-SqCC were also more likely to demonstrate NE differentiation compared to PD-SqCC (p = 0.006). Pure basaloid squamous cell carcinoma (PB-SqCC) experienced poorer disease-free survival (HR = 3.12, p = 0.043) adjusted for stage. Molecular characterization of paired B-SqCC samples demonstrated DEGs implicated in NOTCH signaling, SCLC and pulmonary neuroendocrine differentiation. Hierarchical clustering using discovered DEGs in unpaired B-SqCC samples distinguished tumors based on NE status (p = 0.048). Likewise, clustering The Cancer Genome Atlas (TCGA) samples with DEGs distinguished B-SqCC from SqCC samples (p = 0.0094).

Conclusion

This study provides IHC and molecular evidence of significant NE-differentiation in B-SqCC and demonstrates their aggressive clinical behavior. These findings suggest that B-SqCC are biologically distinct from SqCC and share characteristics with SCLC.

SUBMITTER: Keyhanian K

PROVIDER: S-EPMC9088121 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

Neuroendocrine differentiation distinguishes basaloid variant of lung squamous cell carcinoma.

Keyhanian Kianoosh K Phillips William J WJ Yeung Benjamin S BS Gomes Marcio M Lo Bryan B Sekhon Harmanjatinder S HS

Diagnostic pathology 20220510 1

<h4>Background</h4>Neuroendocrine (NE) differentiation is widely studied in non-small cell lung carcinomas (NSCLC) however, its significance remains unclear in basaloid squamous cell carcinomas (B-SqCC). This study aims to assess the extent of NE differentiation in B-SqCC and characterize the underlying molecular process.<h4>Methods</h4>This study evaluated resected B-SqCC, small cell lung cancer (SCLC) and poorly differentiated SqCC (PD-SqCC) from 2005 to 2020 at the Ottawa Hospital. Samples we ...[more]

PMID: 35538551

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Project description:BackgroundThis study analyzed the clinical features and prognosis of basaloid squamous cell carcinoma of the lung (BSC), and constructed a nomogram to predict the prognoses of patients.MethodsThe information of pure BSC patients was obtained in the Surveillance, Epidemiology, and End Results database between 2004 and 2015. Then, it was evaluated, and compared with the data of lung squamous cell carcinoma (SCC), lung large cell carcinoma (LCC) and lung adenocarcinoma (LAC) patients. Subsequently, we used univariate and multivariate analyses to investigate the independent factors related to the prognoses of patients with BSC and constructed a nomogram to verify the prognoses.ResultsA total of 425 patients diagnosed with BSC were enrolled. Compared with patients with SCC, LCC and LAC, the mean survival time of BSC patients was better than all of them. Compared with SCC, there were significant differences between the characteristics of grade (P < 0.001), total stage (P < 0.001), T stage (P < 0.001), N stage (P < 0.001), M stage (P < 0.001), surgery (P < 0.001), radiotherapy (P < 0.001), and chemotherapy (P < 0.001), while BSC also had significantly different clinical characteristics from LCC and LAC. Univariate and multivariate survival analyses showed that age (P < 0.001), T stage (P < 0.001), N stage (P = 0.009), M stage (P < 0.001), and surgery (P < 0.001) were independent prognostic factors of BSC. The survival of patients undergoing lobectomy was significantly better than sublobar resection, with an OR of 0.389 (0.263-0.578). We constructed a nomogram with a C-index of 0.750 (95% confidence interval) based on the results of multivariate analysis. The calibration curves based on nomogram scores indicated that the nomogram could accurately predict the prognosis of patients.ConclusionsBSC had unique clinical and prognostic features. T stage, N stage, M stage, age, and surgery were independently associated with overall survival (OS). Lobectomy was a relative ideal choice for patients with BSC. The nomogram effectively predicted the OS at 1-, 3-, and 5-years.

Project description:IntroductionNevoid basal cell carcinoma syndrome is a rare autosomal dominant disorder characterized by numerous basal cell carcinomas, odontogenic keratocysts of the jaws and developmental defects. The disorder results from mutations in the PTCH1 gene.Case presentationA 15-year-old boy presented to our dental clinic with multiple jaw cysts. The patient had broad confluent eyebrows, a broad base of the nose, frontal bossing and palmoplantar pits. Examination of the jaw cysts revealed many keratinizing cysts without granular cell layers a finding that raised the suspicion of nevoid basal cell carcinoma. Radiological examinations showed calcification of the falx cerebri, spina bifida, bifid thoracic ribs and frontal bossing. Histopathological examination showed basaloid proliferation in the upper dermis with follicular differentiation surrounded by a loose mucinous stroma and retraction artifacts. These features make it difficult to differentiate between nevoid basal cell carcinoma and basaloid follicular hamartoma, especially the presence of these findings on a non-hairy area. BCL-2 staining was positive in the periphery of the basaloid proliferation, which is typical of basaloid follicular hamartoma, and not in a diffuse pattern, which is typical of nevoid basal cell carcinoma. The proband's siblings and parents were healthy with no family history of this condition in the extended family. Since histology was equivocal and palmoplantar pits are seen in both basaloid follicular hamartoma and nevoid basal cell carcinoma, molecular genetic investigation was necessary to differentiate between the two potential diagnoses. After sequencing the entire PTCH1 gene, we detected a single nucleotide deletion (c.1291delC) in codon 431 of the PTCH protein, which resulted in a premature stop translation at residue 431. This de novo mutation was not detected in both parents and in 100 normal volunteers of matching ethnicity.ConclusionScreening the PTCH1 gene for mutations helped to differentiate between basaloid follicular hamartoma and nevoid basal cell carcinoma and confirmed the diagnosis.

Dataset Information

Neuroendocrine differentiation distinguishes basaloid variant of lung squamous cell carcinoma.

Background

Methods

Results

Conclusion

Publications

Neuroendocrine differentiation distinguishes basaloid variant of lung squamous cell carcinoma.

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