Correlation of TTF-1 immunoexpression and EGFR mutation spectrum in non–small cell lung carcinoma
Background Thyroid transcription factor (TTF-1) is a diagnostic marker expressed in 75%–85% of primary lung adenocarcinomas (ACs). Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene is the most common targetable driver alteration in lung AC. Previo...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Korean Society of Pathologists & the Korean Society for Cytopathology
2021-07-01
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| Series: | Journal of Pathology and Translational Medicine |
| Subjects: | |
| Online Access: | http://www.jpatholtm.org/upload/pdf/jptm-2021-05-10.pdf |
| _version_ | 1818671980044353536 |
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| author | Tripti Nakra Varsha Singh Aruna Nambirajan Prabhat Singh Malik Anant Mohan Deepali Jain |
| author_facet | Tripti Nakra Varsha Singh Aruna Nambirajan Prabhat Singh Malik Anant Mohan Deepali Jain |
| author_sort | Tripti Nakra |
| collection | DOAJ |
| description | Background Thyroid transcription factor (TTF-1) is a diagnostic marker expressed in 75%–85% of primary lung adenocarcinomas (ACs). Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene is the most common targetable driver alteration in lung AC. Previous studies have shown a positive correlation between TTF-1 and EGFR mutation status. We aimed to determine the predictive value of TTF-1 immunoexpression for underlying EGFR mutation status in a large Indian cohort. Methods This retrospective designed study was conducted with medical record data from 2011 to 2020. All cases of primary lung AC and non–small cell lung carcinoma not otherwise specified (NSCLC, NOS) with known TTF-1 expression diagnosed by immunohistochemistry using 8G7G3/1 antibodies and EGFR mutation status diagnosed by quantitative polymerase chain reaction were retrieved, reviewed, and theresults were analyzed. Results Among 909 patient samples diagnosed as lung AC and NSCLC, NOS, TTF-1 was positive in 76.8% cases (698/909) and EGFR mutations were detected in 29.6% (269/909). A strong positive correlation was present between TTF-1 positivity and EGFR mutation status (odds ratio, 3.61; p < .001), with TTF-1 positivity showing high sensitivity (90%) and negative predictive value (87%) for EGFR mutation. TTF-1 immunoexpression did not show significant correlation with uncommon/dual EGFR mutations (odds ratio, 1.69; p = .098). EGFR–tyrosine kinase inhibitor therapy was significantly superior to chemotherapy among EGFR mutant cases irrespective of TTF-1 status; however, no significant differences among survival outcomes were observed. Conclusions Our study confirms a strong positive correlation between TTF-1 expression and common EGFR mutations (exon 19 deletion and exon 21 L858R) in advanced lung AC with significantly high negative predictive value of TTF-1 for EGFR mutations. |
| first_indexed | 2024-12-17T07:32:37Z |
| format | Article |
| id | doaj.art-6168d60e9e5b49dbb47fdfb13976685c |
| institution | Directory Open Access Journal |
| issn | 2383-7837 2383-7845 |
| language | English |
| last_indexed | 2024-12-17T07:32:37Z |
| publishDate | 2021-07-01 |
| publisher | Korean Society of Pathologists & the Korean Society for Cytopathology |
| record_format | Article |
| series | Journal of Pathology and Translational Medicine |
| spelling | doaj.art-6168d60e9e5b49dbb47fdfb13976685c2022-12-21T21:58:27ZengKorean Society of Pathologists & the Korean Society for CytopathologyJournal of Pathology and Translational Medicine2383-78372383-78452021-07-0155427928810.4132/jptm.2021.05.1016980Correlation of TTF-1 immunoexpression and EGFR mutation spectrum in non–small cell lung carcinomaTripti Nakra0Varsha Singh1Aruna Nambirajan2Prabhat Singh Malik3Anant Mohan4Deepali Jain5 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India Department of Pathology, All India Institute of Medical Sciences, New Delhi, India Department of Pathology, All India Institute of Medical Sciences, New Delhi, India Department of Medical Oncology, Dr B.R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India Department of Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences, New Delhi, India Department of Pathology, All India Institute of Medical Sciences, New Delhi, IndiaBackground Thyroid transcription factor (TTF-1) is a diagnostic marker expressed in 75%–85% of primary lung adenocarcinomas (ACs). Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene is the most common targetable driver alteration in lung AC. Previous studies have shown a positive correlation between TTF-1 and EGFR mutation status. We aimed to determine the predictive value of TTF-1 immunoexpression for underlying EGFR mutation status in a large Indian cohort. Methods This retrospective designed study was conducted with medical record data from 2011 to 2020. All cases of primary lung AC and non–small cell lung carcinoma not otherwise specified (NSCLC, NOS) with known TTF-1 expression diagnosed by immunohistochemistry using 8G7G3/1 antibodies and EGFR mutation status diagnosed by quantitative polymerase chain reaction were retrieved, reviewed, and theresults were analyzed. Results Among 909 patient samples diagnosed as lung AC and NSCLC, NOS, TTF-1 was positive in 76.8% cases (698/909) and EGFR mutations were detected in 29.6% (269/909). A strong positive correlation was present between TTF-1 positivity and EGFR mutation status (odds ratio, 3.61; p < .001), with TTF-1 positivity showing high sensitivity (90%) and negative predictive value (87%) for EGFR mutation. TTF-1 immunoexpression did not show significant correlation with uncommon/dual EGFR mutations (odds ratio, 1.69; p = .098). EGFR–tyrosine kinase inhibitor therapy was significantly superior to chemotherapy among EGFR mutant cases irrespective of TTF-1 status; however, no significant differences among survival outcomes were observed. Conclusions Our study confirms a strong positive correlation between TTF-1 expression and common EGFR mutations (exon 19 deletion and exon 21 L858R) in advanced lung AC with significantly high negative predictive value of TTF-1 for EGFR mutations.http://www.jpatholtm.org/upload/pdf/jptm-2021-05-10.pdfegfr mutationlung adenocarcinomanon–small cell lung carcinomathyroid transcription factor-1uncommon mutations |
| spellingShingle | Tripti Nakra Varsha Singh Aruna Nambirajan Prabhat Singh Malik Anant Mohan Deepali Jain Correlation of TTF-1 immunoexpression and EGFR mutation spectrum in non–small cell lung carcinoma Journal of Pathology and Translational Medicine egfr mutation lung adenocarcinoma non–small cell lung carcinoma thyroid transcription factor-1 uncommon mutations |
| title | Correlation of TTF-1 immunoexpression and EGFR mutation spectrum in non–small cell lung carcinoma |
| title_full | Correlation of TTF-1 immunoexpression and EGFR mutation spectrum in non–small cell lung carcinoma |
| title_fullStr | Correlation of TTF-1 immunoexpression and EGFR mutation spectrum in non–small cell lung carcinoma |
| title_full_unstemmed | Correlation of TTF-1 immunoexpression and EGFR mutation spectrum in non–small cell lung carcinoma |
| title_short | Correlation of TTF-1 immunoexpression and EGFR mutation spectrum in non–small cell lung carcinoma |
| title_sort | correlation of ttf 1 immunoexpression and egfr mutation spectrum in non small cell lung carcinoma |
| topic | egfr mutation lung adenocarcinoma non–small cell lung carcinoma thyroid transcription factor-1 uncommon mutations |
| url | http://www.jpatholtm.org/upload/pdf/jptm-2021-05-10.pdf |
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