scholarly journals GPR87 Is an Overexpressed G-Protein Coupled Receptor in Squamous Cell Carcinoma of the Lung

2008 ◽  
Vol 24 (1) ◽  
pp. 41-50 ◽  
Author(s):  
Mathias Gugger ◽  
Richard White ◽  
Susan Song ◽  
Bea Waser ◽  
Renzo Cescato ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
G Protein ◽  
Squamous Cell ◽  
Small Cell Lung Carcinoma ◽  
Treatment Options ◽  
Molecular Structures ◽  
Tissue Samples ◽  
Cell Lung Carcinoma ◽  
G Protein Coupled

Lung cancer is the leading cause of cancer death worldwide. The overall 5-year survival after therapy is about 16% and there is a clear need for better treatment options, such as therapies targeting specific molecular structures. G-protein coupled receptors (GPCRs), as the largest family of cell surface receptors, represent an important group of potential targets for diagnostics and therapy. We therefore used laser capture microdissection and GPCR-focused Affymetrix microarrays to examine the expression of 929 GPCR transcripts in tissue samples of 10 patients with squamous cell carcinoma and 7 with adenocarcinoma in order to identify novel targets in non-small cell lung carcinoma (NSCLC). The relative gene expression levels were calculated in tumour samples compared to samples of the neighbouring alveolar tissue in every patient. Based on this unique study design, we identified 5 significantly overexpressed GPCRs in squamous cell carcinoma, in the following decreasing order of expression: GPR87 > CMKOR1 > FZD10 > LGR4 > P2RY11. All are non-olfactory and GRAFS (glutamate, rhodopsin, adhesion, frizzled/taste2, secretin family) classified. GPR87, LGR4 and CMKOR1 are orphan receptors. GPR87 stands out as a candidate for further target validation due to its marked overexpression and correlation on a mutation-based level to squamous cell carcinoma.

Association of serum level of YKL-40 in patients with squamous cell carcinoma of the head and neck with survival

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5551-5551
Author(s):  
A. Roslind ◽  
J. S. Johansen ◽  
I. J. Christensen ◽  
J. Bentzen ◽  
D. L. Nielsen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Small Cell Lung Carcinoma ◽  
Univariate Analysis ◽  
High Serum ◽  
Cell Lung Carcinoma ◽  
Stage 1

5551 Background: High serum YKL-40 is associated with poor prognosis in breast-, colorectal-, ovarian-, prostate-, small cell lung carcinoma and malignant melanoma. YKL-40 is secreted by cancer cells, macrophages and neutrophils. Its function in cancer is unknown. It may be a growth factor, play a role in angiogenesis or protect against apoptosis. The aim was to examine serum YKL-40 in patients with squamous cell carcinoma of the head and neck (SCCHN). Methods: YKL-40 was determined by ELISA (Quidel, Santa Clara, CA) in serum samples from 138 patients with SCCHN (median age 60, range 44–92 years) before surgery and/or fractionated radiotherapy (total dose of 60–68 Gy, 2-Gy fractions). 42 patients had stage 1, 28 stage 2, 22 stage 3, and 46 stage 4 disease. The median follow-up time was 4.0 years (range 15 days–8.5 years). 91 patients had died. Results: Serum YKL-40 was increased (p < 0.001) in patients with SCCHN (median 120 μg/l, range 25–1848 μg/l) compared to healthy controls (43 μg/l, 20–184 μg/l, n = 245). Serum YKL-40 was elevated in 52% of the patients. Patients with stage 1 disease had lower, but non-significant, serum YKL-40 compared to patients with stage 2–4 disease (median 113 μg/l, range 25–1000 μg/l vs. 139 μg/l, 29–1848 μg/l, p = 0.06). Patients with high serum YKL-40 had significantly shorter survival than patients with normal serum YKL-40 (33 months vs. 74 months, p = 0.01 logrank test). Univariate analysis of serum YKL-40 (log transformed and treated as a continuous covariate) showed significant association with overall survival after start of therapy (HR = 1.4, 95% CI: 1.2–1.7, p = 0.0004). Multivariate Cox analysis including age, stage and serum YKL-40 (log transformed and treated as a continuous variable) showed that stage (stage 3–4 vs. stage 1–2, HR = 3.0, 95% CI: 1.9–4.6, p < 0.0001) and serum YKL-40 (HR = 1.5, 95% CI: 1.2–1.8, p = 0.0003) were independent prognostic variables of overall survival. Conclusions: Serum YKL-40 is a prognostic biomarker of overall survival in SCCHN patients. No significant financial relationships to disclose.

α-Methylacyl CoA Racemase in Pulmonary Adenocarcinoma, Squamous Cell Carcinoma, and Neuroendocrine Tumors: Expression and Survival Analysis

2007 ◽  
Vol 131 (10) ◽  
pp. 1555-1560
Author(s):  
Konstantin Shilo ◽  
Tatiana Dracheva ◽  
Haresh Mani ◽  
Junya Fukuoka ◽  
Isabell A. Sesterhenn ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Large Cell ◽  
Small Cell ◽  
Stage I ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

Abstract Context.—α-Methylacyl CoA racemase (AMACR) is an oxidative enzyme involved in isomeric transformation of fatty acids entering the beta-oxidation pathway. AMACR serves as a useful marker in establishing a diagnosis of prostatic malignancy; however, limited information is available in regard to its presence in pulmonary neoplasms. Objective.—To investigate AMACR expression within a spectrum of lung carcinomas and its correlation with patients' survival. Design.—Four hundred seventy-seven pulmonary carcinomas, including 150 squamous cell carcinomas, 150 adenocarcinomas, 46 typical carcinoids, 31 atypical carcinoids, 28 large cell neuroendocrine carcinomas, and 72 small cell carcinomas, were studied immunohistochemically using tissue microarray–based samples. Results.—Overall, pulmonary tumors were positive for AMACR in a significant percentage (47%) of cases. Among tumor types, 22% of squamous cell carcinoma, 56% of adenocarcinoma, 72% of typical carcinoid, 52% of atypical carcinoid, 70% of large cell neuroendocrine carcinoma, and 51% of small cell lung carcinoma were positive for AMACR. Furthermore, the Kaplan-Meier analysis revealed that the patients with AMACR-positive small cell carcinoma had better survival (19% vs 5% after 5 years, P = .04) than patients with AMACR-negative tumors. Such survival advantage was seen for patients with stage I–II (P = .01) but not stage III–IV small cell carcinomas (P = .58). Conclusions.—These results indicate that, similar to prostate cancer, the overexpression of AMACR frequently occurs in pulmonary carcinomas. Additionally, its positive correlation with outcome of stage I–II small cell lung carcinoma warrants further investigation of the AMACR role in the prognosis of this tumor.

scholarly journals Case Report: Partial Response Following Nivolumab Plus Docetaxel in a Patient With EGFR Exon 20 Deletion/Insertion (p.N771delinsGF) Mutant Lung Adenocarcinoma Transdifferentiated From Squamous Cell Carcinoma

2022 ◽  
Vol 9 ◽  
Author(s):  
Lingling Zhu ◽  
Yanyang Liu ◽  
Honglin Gao ◽  
Jiewei Liu ◽  
Qinghua Zhou ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Lung Adenocarcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Small Cell Lung Carcinoma ◽  
Lung Squamous Cell Carcinoma ◽  
Insertion Mutation ◽  
Cell Lung Carcinoma ◽  
Histological Transformation ◽  
Exon 20

The histological transformation from lung squamous cell carcinoma (LUSC) to lung adenocarcinoma (LUAD) and p. N771delinsGF mutations in EGFR exon 20 (ex20) are exceedingly rare in non–small cell lung carcinoma (NSCLC). EGFR ex20 mutations are insensitive to EGFR tyrosine kinase inhibitors in NSCLC. Here, we present a 76-year-old male smoker harboring LUAD with a novel p. N771delinsGF deletion/insertion mutation in EGFR ex20 transdifferentiating from advanced LUSC after chemoradiotherapy. The patient presented reduced hydrothorax and relieved tightness with the treatment of nivolumab plus docetaxel and carboplatin after the failure of second-line chemotherapy. The case highlights the importance of rebiopsy and molecular retesting after the progression of lung cancer and supports the idea that the combination of immune checkpoint blockade and chemotherapy may be an attractive option for patients with EGFR ex20 mutations associated with LUSC–LUAD transformation.

Expression of programmed death-ligand 1 protein in pulmonary squamous cell carcinoma correlates with tumour necrosis but not with tumour differentiation

2021 ◽  
pp. jclinpath-2020-207171
Author(s):  
Vladimír Tancoš ◽  
Anna Farkašová ◽  
Zuzana Kviatkovská ◽  
Marián Grendár ◽  
Alena Líšková ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumour Necrosis ◽  
Small Cell Lung Carcinoma ◽  
Tumour Mass ◽  
Cell Lung Carcinoma ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Tumour Differentiation

AimsPulmonary squamous cell carcinoma (SqCC) represents the second most common non-small cell lung carcinoma type. The mechanisms which regulate programmed death ligand 1 (PD-L1) expression in this form of lung cancer are not fully elucidated yet.MethodsWe immunohistochemically determined the level of PD-L1 expression using the Tumour Proportion Score system in surgical resections of 133 patients with pulmonary SqCC. The results from PD-L1 immunohistochemistry were analysed in relation to tumour differentiation and the presence of necrotic areas comprising at least 20% of the tumour mass.ResultsNo significant differences in terms of PD-L1 expression were found between SqCC subtypes as defined by the current WHO classification: better differentiated, keratinising tumours (12/24, 50.0 %) compared with less differentiated, non-keratinising and basaloid forms (62/109, 56.9 %) were PD-L1 positive in a comparable proportion of cases (p=0.1903). Contrary to that, SqCCs with the presence of necrosis (51/61, 83.6 %) had significantly more PD-L1-positive cases (p<0.001) compared with SqCCs without necrotic areas (23/72, 32.0 %)ConclusionsWe demonstrated that PD-L1 expression in pulmonary SqCCs does not correlate with the traditionally defined degree of differentiation of these tumours. On the other hand, we found a significant association between the positive result of PD-L1 immunohistochemistry and tumour necrosis. Further investigation regarding the role of hypoxic pathways as presumable inducers of PD-L1 expression in pulmonary SqCCs might contribute to the understanding of this phenomenon.

There is still a role for cytology in the ‘liquid biopsy’ era. A lesson from a TKI-treated patient showing adenocarcinoma to squamous cell carcinoma transition during disease progression

2017 ◽  
Vol 70 (9) ◽  
pp. 798-802 ◽  
Author(s):  
Eduardo Clery ◽  
Pasquale Pisapia ◽  
Salvatore Feliciano ◽  
Elena Vigliar ◽  
Antonio Marano ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Squamous Cell ◽  
Liquid Biopsy ◽  
Treated Patient ◽  
Small Cell Lung Carcinoma ◽  
Resistance Mechanisms ◽  
Blood Draw ◽  
Cell Lung Carcinoma

Non-small cell lung carcinoma harbouring epidermal growth factor receptor (EGFR) mutation, usually progress after an initial response to tyrosine-kinase inhibitors (TKI). Liquid biopsy enables with a simple blood draw the accurate detection ofEGFRp.T790M mutation, the most common resistance mechanism, avoiding the more invasive tissue re-biopsy. However, in a subset of cases, resistance mechanisms are more complex featuring both genetic and morphological changes. Here we report the case of a 67 years-old woman, affected by anEGFRmutated lung adenocarcinoma and treated by TKI. At disease progression, the patient developed a morphological transition to squamous cell carcinoma in association to the arising of aPIK3CAp.E542K mutant subclone. This case illustrates that, even in the “liquid biopsy” era, cytology can have still a role by providing an overall assessment of both morphology and genetic TKI resistance mechanisms.

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