Evaluation of Napsin A, Cytokeratin 5/6, p63, and Thyroid Transcription Factor 1 in Adenocarcinoma Versus Squamous Cell Carcinoma of the Lung

Context.—The distinction of lung adenocarcinoma from other types of primary lung malignancies is important clinically. Accurate morphologic classification is often hindered because 70% of lung cancers are diagnosed on limited fine-needle aspiration or transbronchial biopsy specimens. Although thyroid transcription factor 1 (TTF-1) has historically been the most specific marker for lung adenocarcinoma, a relatively new marker, napsin A, has recently been shown to be more sensitive and specific than TTF-1. Objective.—To find the most cost-effective panel to reliably distinguish lung adenocarcinoma from squamous cell carcinoma. Design.—A total of 291 lung cancers were evaluated morphologically (197 adenocarcinomas [75%]; 66 squamous cell carcinomas [25%]; 28 cases could not be classified into either and were dropped). Immunohistochemistry for napsin A, Cytokeratin 5/6, p63, and TTF-1 was performed on a formalin-fixed tissue microarray obtained from Toyama, Japan. Cases were scored as positive or negative against a negative control. Results.—Napsin A had 83% sensitivity and 98% specificity and TTF-1 had 60% sensitivity and 98% specificity for adenocarcinoma. Cytokeratin 5/6 had 53% sensitivity and 96% specificity and p63 had 95% sensitivity and 86% specificity for squamous cell carcinoma. A panel of napsin A and p63 has a specificity of 94% and a sensitivity of 96% for distinguishing adenocarcinoma from squamous cell carcinoma. Conclusions.—The source of the antibody is important in avoiding false-negative results. The most cost-effective tissue-preserving panel for small biopsy specimens in the differential diagnosis of lung adenocarcinoma versus squamous cell carcinoma is a combination of p63 and napsin A.

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Expressions of Thyroid Transcription Factor-1, Napsin A, p40, p63, CK5/6 and Desmocollin-3 in Non-Small Cell Lung Cancer, as Revealed by Imprint Cytology Using a Malinol-Based Cell-Transfer Technique

Acta Cytologica ◽

10.1159/000442659 ◽

2015 ◽

Vol 59 (6) ◽

pp. 457-464 ◽

Cited By ~ 3

Author(s):

Toshiaki Kawai ◽

Susumu Tominaga ◽

Sadayuki Hiroi ◽

Koji Kameda ◽

Sho Ogata ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Small Cell ◽

Imprint Cytology ◽

Small Cell Lung ◽

Thyroid Transcription Factor 1 ◽

Thyroid Transcription Factor ◽

Napsin A ◽

Transcription Factor 1

Background: The introduction of new therapies has made it important to differentiate between adenocarcinoma and squamous cell carcinoma. To allow the use of various immunocytochemical stains on limited materials, we tried transferring cells from a given smear to multiple slides. Using touch-preparation samples of 215 surgically resected non-small cell lung carcinomas of confirmed histologic classification (adenocarcinoma,n = 101; squamous cell carcinoma,n = 114), we performed immunocytochemistry for thyroid transcription factor-1, napsin A, p40, p63, CK5/6 and desmocollin-3, and compared cytologic staining results with the corresponding resection. Methods: We examined: (a) the expressions of the above 6 antibodies on cells transferred from touch imprints of resected specimens, the extent of staining being considered positive if more than 5% of the area was stained, and (b) the sensitivity, specificity, positive predictive value and negative predictive value for each antibody. Results: The histologic corresponding rate with Papanicolaou staining was only 73%. Regarding the differentiation of adenocarcinoma from squamous cell carcinoma, the sensitivity and specificity for napsin A in adenocarcinoma were 80 and 97%, respectively, while those for p40 in squamous cell carcinoma were 84 and 98%, respectively. Conclusion: The immunocytochemical expressions of napsin A and p40 in imprint cytology seem to be of great utility for the accurate histological differentiation of lung cancers.

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Tissue-Preserving Antibody Cocktails to Differentiate Primary Squamous Cell Carcinoma, Adenocarcinoma, and Small Cell Carcinoma of Lung

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2012-0635-oa ◽

2013 ◽

Vol 137 (9) ◽

pp. 1274-1281 ◽

Cited By ~ 40

Author(s):

Alan F. Brown ◽

Deepika Sirohi ◽

Junya Fukuoka ◽

Philip T. Cagle ◽

Maria Policarpio-Nicolas ◽

...

Keyword(s):

Transcription Factor ◽

Cell Carcinoma ◽

Small Cell ◽

Lung Cancers ◽

Thyroid Transcription Factor 1 ◽

Thyroid Transcription Factor ◽

Napsin A ◽

Cytokeratin 5 ◽

Transcription Factor 1 ◽

Desmoglein 3

Context.—With the availability of cell type–specific therapies, differentiating primary lung squamous cell carcinomas (SCCs) and adenocarcinomas (ACAs) has become important. The limitations of small sample size and the need to conserve tissue for additional molecular studies necessitate the use of sensitive and specific marker panels on a single slide. Objective.—To distinguish SCC from ACA and small cell carcinoma (SmCC) of lung using 2 novel tissue-conserving cocktails. Design.—We compared two antibody cocktails, desmoglein 3 + cytokeratin 5/napsin A and p40/thyroid transcription factor 1 (Biocare Medical, Concord, California) in diagnosing SCC and ACA of the lung on tissue microarray, cytology, and surgical specimens. Both lung and nonlung tissue were evaluated on an 1150-core tissue microarray that contained 200 lung cancers. A microarray of 35 SmCCs and 5 small cell SCCs was also evaluated. Results.—A cocktail of desmoglein 3 + cytokeratin 5/napsin A provided diagnostic accuracy in lung cancers with a sensitivity and specificity of 100% in SCCs and a sensitivity of 86% and a specificity of 100% in ACAs. A p40/thyroid transcription factor 1 cocktail showed p40 to have a specificity of 92% and a sensitivity of 93% in SCCs, whereas thyroid transcription factor 1 had a specificity of 100% and a sensitivity of 77% in ACAs. Cell blocks of fine-needle aspiration cytology compared with corresponding surgical (n = 20) specimens displayed similar findings. The p40 was useful in differentiating bladder from prostate carcinoma with 88% sensitivity. Isolated carcinomas from nonlung tissues were desmoglein 3 + cytokeratin 5 positive. Napsin A was positive in 22% of renal tumors as previously observed. Both cocktails were excellent in differentiating SmCCs and small cell SCCs because none of the SmCCs stained with p40. Conclusions.—Both antibody cocktails are excellent in differentiating primary lung ACA from SCC, as well as excluding SmCC and ACAs from all other sites on small specimens. A cocktail of desmoglein 3 + cytokeratin 5/napsin A is slightly superior compared with p40/thyroid transcription factor 1 cocktail.

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Significant Expression of Thyroid Transcription Factor-1 in Pulmonary Squamous Cell Carcinoma Detected by SPT24 Monoclonal Antibody and CSA-II System

Applied Immunohistochemistry & Molecular Morphology ◽

10.1097/pai.0b013e31828acad2 ◽

2014 ◽

Vol 22 (2) ◽

pp. 119-124 ◽

Cited By ~ 4

Author(s):

Kenji Kashima ◽

Hisashi Hashimoto ◽

Haruto Nishida ◽

Motoki Arakane ◽

Naomi Yada ◽

...

Keyword(s):

Monoclonal Antibody ◽

Squamous Cell Carcinoma ◽

Transcription Factor ◽

Cell Carcinoma ◽

Squamous Cell ◽

Thyroid Transcription Factor 1 ◽

Thyroid Transcription Factor ◽

Significant Expression ◽

Transcription Factor 1

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The Regulators Associated With N6-Methyladenosine in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma Reveal New Clinical and Prognostic Markers

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.741521 ◽

2021 ◽

Vol 9 ◽

Author(s):

Shuzhen Tan ◽

Zesong Li ◽

Kai Li ◽

Yingqi Li ◽

Guosheng Liang ◽

...

Keyword(s):

Lung Cancer ◽

Squamous Cell Carcinoma ◽

Lung Adenocarcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Prognostic Markers ◽

Cox Regression ◽

Lung Squamous Cell Carcinoma ◽

Lung Cancers ◽

Pathological Characteristics

N6-methyladenosine (m6A) methylation is of significant importance in the initiation and progression of tumors, but how specific genes take effect in different lung cancers still needs to be explored. The aim of this study is to analyze the correlation between the m6A RNA methylation regulators and the occurrence and development of lung cancer. The data of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were obtained through the TCGA database. We systematically analyzed the related pathological characteristics and prognostic factors by applying univariate and multivariate Cox regression, as well as LASSO Cox regression. Some of 23 m6A regulators are identified as having high expression in lung cancer. In addition, risk score has been shown to be an independent prognostic factor in lung cancer. Our research not only fully reveals that m6A regulators and clinical pathological characteristics are potentially useful with respect to survival and prognosis in different lung tumors but also can lay a theoretical root for the treatment for lung cancer—notably, to point out a new direction for the development of treatment.

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Females and Males Show Differences in Early-Stage Transcriptomic Biomarkers of Lung Adenocarcinoma and Lung Squamous Cell Carcinoma

Diagnostics ◽

10.3390/diagnostics11020347 ◽

2021 ◽

Vol 11 (2) ◽

pp. 347

Author(s):

Quewang Liu ◽

Yueying Wang ◽

Meiyu Duan ◽

Yusi Fan ◽

Xingyuan Pan ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Lung Adenocarcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Early Stage ◽

Lung Squamous Cell Carcinoma ◽

Disease Diagnosis ◽

Diagnostic Model ◽

Lung Cancers ◽

Incidence And Mortality

The incidence and mortality rates of lung cancers are different between females and males. Therefore, sex information should be an important part of how to train and optimize a diagnostic model. However, most of the existing studies do not fully utilize this information. This study carried out a comparative investigation between sex-specific models and sex-independent models. Three feature selection algorithms and five classifiers were utilized to evaluate the contribution of the sex information to the detection of early-stage lung cancers. Both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) showed that the sex-specific models outperformed the sex-independent detection of early-stage lung cancers. The Venn plots suggested that females and males shared only a few transcriptomic biomarkers of early-stage lung cancers. Our experimental data suggested that sex information should be included in optimizing disease diagnosis models.

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Dual color multiplex TTF-1 + Napsin A and p63 + CK5 immunostaining for subcategorizing of poorly differentiated pulmonary non-small carcinomas into adenocarcinoma and squamous cell carcinoma in fine needle aspiration specimens

CytoJournal ◽

10.4103/1742-6413.94570 ◽

2012 ◽

Vol 9 ◽

pp. 10 ◽

Cited By ~ 18

Author(s):

Seema Sethi ◽

Lili Geng ◽

Vinod B Shidham ◽

Pamela Archuletta ◽

Sudeshna Bandyophadhyay ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Lung Adenocarcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Fine Needle Aspiration ◽

Needle Aspiration ◽

Fine Needle ◽

Dual Color ◽

Napsin A ◽

Poorly Differentiated

Background: The distinction of lung adenocarcinoma (ADC) from squamous cell carcinoma (SCC) has important therapeutic implications. Napsin A is a recently developed marker, which has shown high specificity for lung tissue in the surgical pathology specimens. In this study, we have evaluated whether the use of a panel of novel multiplex cocktails of TTF-1 + Napsin A and p63 + CK5 for dual color immunostaining will improve the diagnostic accuracy of lung adenocarcinoma and squamous cell carcinoma in fine needle aspiration (FNA) specimens, usually with relatively scant microfragments of diagnostic material. Materials and Methods: Formalin-fixed, paraffin-embedded, adequately cellular FNA cell blocks with a confirmed diagnosis of either ADC (n = 22), SCC (n = 20) or poorly differentiated carcinoma (PDC; n = 7), from a total of 49 consecutive cases, were studied. All these cases had subsequently confirmed diagnosis in biopsies or resection specimens. The sections were immunostained with two color methods of TTF-1 + Napsin A and p63 + CK5 multiplex cocktails. The presence of one or more unequivocal individual tumor cells with convincing brown nuclear TTF-1 and red cytoplasmic Napsin A staining, and cells with brown nuclear p63 and membranous / cytoplasmic CK5 staining were interpreted as ‘positive’. Results: All 20 FNA cell blocks from SCC cases were positive for dual stain p63 + CK5 and negative for dual stain TTF-1 + Napsin A. The sensitivity and specificity of the dual immunoexpressions of p63 + CK5 for SCC of lung FNAs were both 100%. All 22 ADC cases were positive with dual stain of TTF-1 + Napsin A and negative for dual stain of p63 + CK5. On follow-up of the surgical pathology specimens, 22 cases were confirmed as ADC. The sensitivity of the dual immunoexpression of TTF-1 + Napsin A for ADC of lung FNAs was 100% and the specificity was also 100%. Of the seven PDC cases, five cases that were positive for dual stain p63 + CK5 and negative for dual stain TTF-1 + Napsin A could be categorized as SCC. Two of the seven (2 / 7) PDC cases were positive for dual stain TTF-1 + Napsin A and negative for dual stain p63 + CK5, consistent with ADC. Conclusions: Simultaneous coordinate or individual immunostaining for Napsin A / TTF-1 in ADC and p63 / CK5 in SCC demonstrated high sensitivity and specificity. The panel with multiplex Napsin A / TTF-1 and p63 / CK5 dual color immunostains could specifically subcategorize PDC into ADC and SCC in lung FNA specimens. Multiplex dual color Napsin A / TTF-1 and p63 / CK5 immunostaining is especially recommended for evaluation of FNA specimens with relatively scant cellularity.

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Cost-effectiveness of pembrolizumab for treatment of platinum-resistant recurrent or metastatic head and neck squamous cell carcinoma in China: an economic analysis based on a randomised, open-label, phase III trial

BMJ Open ◽

10.1136/bmjopen-2020-038867 ◽

2020 ◽

Vol 10 (12) ◽

pp. e038867 ◽

Cited By ~ 1

Author(s):

Wenxiu Xin ◽

Haiying Ding ◽

Qilu Fang ◽

Xiaowei Zheng ◽

Yinghui Tong ◽

...

Keyword(s):

Sensitivity Analysis ◽

Squamous Cell Carcinoma ◽

Cost Effectiveness ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Probabilistic Sensitivity Analysis ◽

Cost Effective ◽

Platinum Resistant ◽

The Cost

BackgroundPembrolizumab was recently demonstrated to have survival benefit in patients with recurrent or metastatic head and neck squamous cell carcinoma (r/mHNSCC). However, the cost-effectiveness of pembrolizumab versus chemotherapy in China remains uncertain.ObjectiveThis analysis aimed to describe the cost-effectiveness of pembrolizumab versus standard-of-care (SOC) therapy in r/mHNSCC in China.DesignA Markov model consisting of three health states (stable, progressive and dead) was developed to compare the cost and effectiveness of pembrolizumab with SOC in platinum-resistant r/mHNSCC. Model inputs for transition probabilities and toxicity were collected from the KEYNOTE-040 trial, while health utilities were estimated from a literature review. Cost data were acquired for the payer’s perspective in China. Costs and outcomes were discounted at an annual rate of 3.0%. Sensitivity analyses were conducted to test the uncertainties surrounding model parameters.Outcome measuresThe primary outcome was incremental cost-effectiveness ratios (ICERs), which were calculated as the cost per quality-adjusted life years (QALYs).ResultsThe total mean cost of pembrolizumab and SOC was US$45 861 and US$41 950, respectively. As for effectiveness, pembrolizumab yielded 0.31 QALYs compared with 0.25 QALYs for SOC therapy. The ICER for pembrolizumab versus SOC was US$65 186/QALY, which was higher than the willingness-to-pay threshold (WTP) of US$28 130/QALY in China. The univariate sensitivity analysis indicated that utility values for progressive state, probability from stable to progressive in the SOC group, as well as cost of pembrolizumab were the three most influential variables on ICER. The probabilistic sensitivity analysis demonstrated that standard therapy was more likely to be cost-effective compared with pembrolizumab at a WTP value of US$28 130/QALY. Results were robust across both univariate analysis and probabilistic sensitivity analysis.ConclusionsPembrolizumab is not likely to be a cost-effective strategy compared with SOC therapy in patients with platinum-resistant r/mHNSCC in China.Trial registration numberNCT02252042; Post-results.

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