<scp>KRAS</scp> mutation is predictive of outcome in patients with pulmonary sarcomatoid carcinoma

Mehrad, Mitra; Roy, Somak; LaFramboise, William A.; Petrosko, Patti; Miller, Caitlyn; Incharoen, Pimpin; Đačić, Sanja

doi:10.1111/his.13505

Cited by 34 publications

(38 citation statements)

References 39 publications

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“…84 Similarly, Mehrad and colleagues reported a significant correlation of KRAS mutations with worse patients' outcome. 86 We also showed that the presence of KRAS mutations significantly correlates with increased PD-L1 expression suggesting a possible correlation, to be further investigated, between these mutations and response to immunotherapy. 99 These results together with the recent emerging MEK inhibitors may imply a potential value of KRAS mutations as relevant predictive markers in orienting PSC tailored treatment.…”

Section: Clinical Impact Of Psc Molecular Profilingmentioning

confidence: 56%

“…The first clues about the genetic landscape of PSC became available only in the most recent years. [81][82][83][84][85][86] The raise and rapid expansion of the new sequencing techniques, together with the collection of relatively large series of PSC samples available for the analysis have represented major turning points in getting clues into the genetic assets of these tumors.…”

Section: Recent Insights Into Psc Genetic and Transcriptional Featuresmentioning

confidence: 99%

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Approaches to Tumor Classification in Pulmonary Sarcomatoid Carcinoma

Baldovini¹,

Rossi²,

Ciarrocchi³

2019

LCTT

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Pulmonary sarcomatoid carcinoma (PSC) is a heterogeneous category of primary lung cancer accounting from 0.3% to 3% of all primary lung malignancies. According to the most recent 2015 World Health Organization (WHO) classification, PSC includes several different variants of malignant epithelial tumors (carcinomas) histologically mimicking sarcomas showing or entirely lacking a conventional component of non-small cell lung cancer (NSCLC). Thus, this rare subheading of lung neoplasms includes pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, pulmonary blastoma, and carcinosarcoma. A diagnosis of PSC may be suspected on small biopsy or cytology, but commonly requires a surgical resection to reach a conclusive definition. The majority of patients with PSC consists of elderly, smoking men with a large, peripheral mass characterized by well-defined margins. However, presentation with a central, polypoid endobronchial lesion is well-documented, particularly in pleomorphic carcinoma and carcinosarcoma showing a squamous cell carcinoma component. As expected, PSC may pose diagnostic problems and immunohistochemistry is largely used when pathologists deal these tumors in routine practice. Indeed, PSC tends to overexpress molecules associated with the epithelial-to-mesenchymal transition, such as vimentin, but the panel of immunostains also includes epithelial markers (cytokeratins, EMA), TTF-1, p40 and negative markers (e.g., melanocytic, mesothelial and sarcoma-related primary antibodies). Although rare, PSC has increased their interest among oncologist community for different reasons: a. identification of the epithelial-to-mesenchymal phenomenon as a major mechanism of secondary resistance to tyrosine kinase inhibitors; b. over-expression of PD-L1 and effective treatment with immunotherapy; c. identification of c-MET exon 14 skipping mutation representing an effective target to crizotinib and other specific inhibitors. In this review, the feasibility of the diagnosis of PSC, its differential diagnosis and novel molecular findings characterizing this group of lung tumor are discussed.

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Section: Clinical Impact Of Psc Molecular Profilingmentioning

confidence: 56%

Section: Recent Insights Into Psc Genetic and Transcriptional Featuresmentioning

confidence: 99%

Approaches to Tumor Classification in Pulmonary Sarcomatoid Carcinoma

Baldovini¹,

Rossi²,

Ciarrocchi³

2019

LCTT

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“…Copy number analyses have demonstrated loss of RB1, ATM and gains in EGFR. However, most PSCs have un‐targetable TP53 and KRAS mutations . Of note, MET exon 14 skipping has been reported to be associated with PSCs.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Sarcomatoid carcinoma in cytology: Report of a rare entity presenting in pleural and pericardial fluid preparations

Basu

Moreira

Simms

et al. 2019

Diagnostic Cytopathology

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Sarcomatoid carcinoma is rarely found in pleural or pericardial fluid, with very few cases published to date. Here, we describe a 59-year-old female who presented with cough persisting for 5 months.Chest CT scan revealed a 6.0 cm cavitary mass in the left lung base with bulky mediastinal and hilar lymphadenopathy. An additional 1.2 cm right adrenal mass was seen and was suspicious for metastatic disease. The patient developed dyspnea, tachycardia, pleuritic chest pain and generalized weakness and was admitted to the hospital. She was found to have pleural and pericardial effusions, which were drained and sent to cytology. The fluid revealed enlarged highly pleomorphic malignant cells, some displaying multinucleation with irregular nuclear borders, coarse chromatin and prominent nucleoli. Tumor cells were positive for CK7 and Vimentin and negative for MOC-31, Ber-EP4, B72.3, Sox10, Melan-A, TTF-1, Napsin-A and CK20. A concurrent surgical biopsy of the tumor mass displayed immunopositivity for AE1/AE3 and CAM5.2. The tumor was negative for p40, TTF-1, calretinin, D2-40 and STAT6. A diagnosis of sarcomatoid carcinoma with giant cells and spindle cells was rendered. Sarcomatoid carcinomas of the lung are very uncommon consisting of 1% of nonsmall-cell lung carcinomas and are even more unusual in cytology specimens. Despite its rarity, it is important to keep this entity in mind in the differential diagnosis of a fluid specimen with bizarre nuclear atypia and the above staining pattern. K E Y W O R D Scytology, pulmonary sarcomatoid carcinoma

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“…In addition, KRAS (30-40% of patients) and MET genes (13-20%) are the most common driver oncogene mutations noted in PSC (7). However, targetable mutations in PSC are less frequent than in NSCLC with adenocarcinoma histology, with EGFR mutations reported in 8-22% cases in various studies (7,(9)(10)(11). The efficacy of EGFR tyrosine kinase inhibitors (TKI) in PSC has also varied between studies, and was inferior when compared to adenocarcinoma (7).…”

Section: Discussionmentioning

confidence: 99%

Alk1 gene rearranged pulmonary sarcomatoid carcinoma masquerading as tuberculosis in a young male

Sahay

Kumar²,

Janu³

et al. 2020

TJPATH

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Pulmonary sarcomatoid carcinoma is rare, with limited treatment options and poor prognosis. In contrast to other non small cell lung carcinomas, not much is known about its molecular biology. In an endemic country like India, lung cancer is often masked by tuberculosis and presents in advanced stages. We report here an unusual case of pulmonary sarcomatoid carcinoma, in a young non-smoker male, who had co-existent tuberculosis masking and delaying the diagnosis of malignancy. On molecular study, the tumor showed ALK gene rearrangement, both by immunohistochemistry and fluorescence in-situ hybridization, which has been reported only twice previously. Presence of ALK gene rearrangements in sarcomatoid carcinoma has significant therapeutic implications and potential for altering the prognosis of this fatal disease. Hence we recommend performing ALK gene rearrangement analysis in all cases of sarcomatoid lung carcinomas. The report discusses the diagnostic approach and provides insight into the molecular pathogenesis of this exceedingly rare malignancy.

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KRAS mutation is predictive of outcome in patients with pulmonary sarcomatoid carcinoma

Abstract: Potentially targetable mutations can be identified in a subset of PSC, although most tumours harbour currently untargetable prognostically adverse TP53 and KRAS mutations.

Cited by 34 publications

References 39 publications

<p>Approaches to Tumor Classification in Pulmonary Sarcomatoid Carcinoma</p>

<p>Approaches to Tumor Classification in Pulmonary Sarcomatoid Carcinoma</p>

Sarcomatoid carcinoma in cytology: Report of a rare entity presenting in pleural and pericardial fluid preparations

Alk1 gene rearranged pulmonary sarcomatoid carcinoma masquerading as tuberculosis in a young male

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