Journal of Pathology and Translational Medicine

Case Study

TTF1-positive SMARCA4/BRG1 deficient lung adenocarcinoma: Anurag Mehta, Himanshi Diwan, Divya Bansal, Manoj Gupta; J Pathol Transl Med. 2022;56(1):53-56. Published online November 16, 2021; DOI: https://doi.org/10.4132/jptm.2021.09.16

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SMARCA4/BRG1-deficient lung adenocarcinoma (SD-LUAD) is being recognized as a distinct subtype based on subtle differences in its clinical, morphological, and immunophenotypic attributes compared to other non–small cell lung carcinomas. We present here a case of SD-LUAD with curious thyroid transcription factor 1 (TTF1) expression in a morphologically heterogenous lung adenocarcinoma. The better differentiated area showed preservation of TTF1 expression, and a poorly differentiated tumor had loss of TTF1 expression with universal BRG1 loss.

Citations

Citations to this article as recorded by

SMARCA4-deficient Non–small Cell Lung Cancer on 18F-FDG PET/CT
Tao Liu, Hengshan Ji, Siyuan Jiang, Rongxin Qi, Xiaodie Zhou, Jingjing Sun, Jiang Wu
Clinical Nuclear Medicine Open.2025;[Epub] CrossRef
One Case of Non-Small Cell Lung Cancer with SMARCA4 Deletion Was Reported
允龙宋
Medical Diagnosis.2024; 14(01): 137. CrossRef
Delineation of a SMARCA4-specific competing endogenous RNA network and its function in hepatocellular carcinoma
Lei Zhang, Ting Sun, Xiao-Ye Wu, Fa-Ming Fei, Zhen-Zhen Gao
World Journal of Clinical Cases.2022; 10(29): 10501. CrossRef
Novel germline SMARCA4 mutation in Small Cell Carcinoma of the Ovary, Hypercalcemic Type
Anurag Mehta, Himanshi Diwan, Diksha Karki, Divya Bansal, Meenakshi Kamboj, Anila Sharma, Shrinidhi Nathany, Sakshi Mattoo, Dushyant Kumar
Current Problems in Cancer: Case Reports.2022; 8: 100205. CrossRef

Original Articles

Correlation of TTF-1 immunoexpression and EGFR mutation spectrum in non–small cell lung carcinoma: Tripti Nakra, Varsha Singh, Aruna Nambirajan, Prabhat Singh Malik, Anant Mohan, Deepali Jain; J Pathol Transl Med. 2021;55(4):279-288. Published online July 8, 2021; DOI: https://doi.org/10.4132/jptm.2021.05.10

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Abstract PDF

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 the
results
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.

Citations

Citations to this article as recorded by

Baseline retinoblastoma transcriptional corepressor 1 (Rb1) functional inactivation is a pre-requisite but not sufficient for small-cell histological transformation in epidermal growth factor receptor (EGFR) mutant lung adenocarcinomas post-tyrosine kinas
Aruna Nambirajan, Amber Rathor, Hemavathi Baskarane, Anju GS, Sachin Khurana, Somagattu Sushmitha, Aparna Sharma, Prabhat Singh Malik, Deepali Jain
Virchows Archiv.2025;[Epub] CrossRef
Mutation profile and programmed death ligand 1 status of patients with non‐small cell lung cancer diagnosed with “adenocarcinoma” and “non‐small cell carcinoma favor adenocarcinoma”
Naoko Shigeta, Tomoyuki Yokose, Shuji Murakami, Tetsuya Isaka, Kanako Shinada, Emi Yoshioka, Atsuya Narita, Kengo Katakura, Tetsuro Kondo, Terufumi Kato, Takuya Nagashima, Haruhiro Saito, Hiroyuki Ito
Thoracic Cancer.2024; 15(6): 458. CrossRef
Significance of NKX2-1 as a biomarker for clinical prognosis, immune infiltration, and drug therapy in lung squamous cell carcinoma
Huiyue Lin, Juyong Wang, Qing Shi, Minmin Wu
PeerJ.2024; 12: e17338. CrossRef
TTF-1 is a highly sensitive but not fully specific marker for pulmonary and thyroidal cancer: a tissue microarray study evaluating more than 17,000 tumors from 152 different tumor entities
Katharina Möller, Tayyaba Gulzar, Maximilian Lennartz, Florian Viehweger, Martina Kluth, Claudia Hube-Magg, Christian Bernreuther, Ahmed Abdulwahab Bawahab, Ronald Simon, Till S. Clauditz, Guido Sauter, Ria Schlichter, Andrea Hinsch, Simon Kind, Frank Jac
Virchows Archiv.2024; 485(5): 815. CrossRef
Identifying immunohistochemical biomarkers panel for non-small cell lung cancer in optimizing treatment and forecasting efficacy
Xiaoya Zhang, Junhong Meng, Mingyue Gao, Cheng Gong, Cong Peng, Duxian Liu
BMC Cancer.2024;[Epub] CrossRef
Expression landscapes in non-small cell lung cancer shaped by the thyroid transcription factor 1
Herdee Gloriane C. Luna, Marcelo Severino Imasa, Necy Juat, Katherine V. Hernandez, Treah May Sayo, Gloria Cristal-Luna, Sheena Marie Asur-Galang, Mirasol Bellengan, Kent John Duga, Bien Brian Buenaobra, Marvin I. De los Santos, Daniel Medina, Jamirah Sam
Lung Cancer.2023; 176: 121. CrossRef
Malignant pleural effusion cell blocks are reliable resources for PD-L1 analysis in advanced lung adenocarcinomas: a concordance study with matched histologic samples
Swati Mahajan, Aruna Nambirajan, Ishan Gupta, Nalini Gupta, Parikshaa Gupta, Deepali Jain
Journal of the American Society of Cytopathology.2022; 11(5): 253. CrossRef
Clinicopathologic Features and Molecular Biomarkers as Predictors of Epidermal Growth Factor Receptor Gene Mutation in Non-Small Cell Lung Cancer Patients
Lanlan Liu, Xianzhi Xiong
Current Oncology.2021; 29(1): 77. CrossRef

Immunoexpressions of Thyroid Transcription Factor-1 and bcl-2 in Congenital Cystic Adenomatoid Malformation.: Na Rae Kim, Dong Hoon Kim, Gou Young Kim, Dae Shick Kim, Joungho Han; Korean J Pathol. 2003;37(1):10-14.

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Abstract PDF: BACKGROUND
Congenital cystic adenomatoid malformation (CCAM) is a congenital abnormality of branching morphogenesis of the lung. Thyroid transcription factor-1 (TTF-1) is detected in human respiratory epithelial cells from 11 weeks of gestation, and at full term, TTF-1 expression is confined within type II epithelial cells and in some respiratory nonciliated bronchiolar epithelial cells. Immunoexpression of bcl-2 is intimately related to apoptosis during the development.
METHODS
To elucidate the nature of the lesion, TTF-1 expression was evaluated in twenty-four cases of CCAM (eight cases of type 1 and sixteen cases of type 2) along with immunostaining for bcl-2. For the control group, four cases of fetal lungs (19 week-, 21 week-, 27 week- and 40 week-gestational age) were also evaluated. In all cases of CCAM, TTF-1 was detected in the nuclei of epithelial cells lining the cysts.
RESULTS
TTF-1 was expressed in the majority of the bronchiolar-like epithelial cells of the cysts in CCAM types 1, and 2, where almost 100% of the lining cells of the cysts were TTF-1 positive with variable intensity, while negative TTF-1 expressions were found in the alveolar-like epithelium of the adjacent alveoli or distal nonciliated bronchi. For bcl-2 immunostaining, no lining epithelial cells of the cysts were stained except for the infiltrating lymphocytes. In the control group, strong immunoreactivities found in early fetal stages were absent in the full-term aged lung (40 gestational weeks).
CONCLUSION
These results support the hypothesis that CCAM types 1 and 2 reflect the abnormalities in lung morphogenesis and differentiation that are distinct from those for normally developed alveolar epithelium or adjacent bronchial epithelium, thus retaining the abnormal TTF-1 immunoreactions. Though restricted to CCAM types 1 and 2 in this study, CCAM might be related to TTF-1 rather than apoptosis in the morphogenesis of the developing lung.

Case Report

Uterine Cervical Large Cell Neuroendocrine Carcinoma Concurrent with High Grade Squamous Intraepithelial Neoplasia: A Case Report.: Yun Kyung Kang, Jae Whoan Koh; Korean J Pathol. 2008;42(6):389-392.

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Abstract PDF: Large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is a rare and aggressive malignancy. We report a case of uterine cervical LCNEC concurrent with high grade squamous intraepithelial neoplasia (HG-SIN). The LCNEC expressed chromogranin A and thyroid transcription factor 1 (TTF1). The HG-SIN was negative for these markers. Human papillomavirus (HPV) type 18 was positive in LCNEC whereas both type 16 and 18 were positive in HG-SIN by nested polymerase chain reaction. This case showed TTF1 positivity nonetheless diagnosed as a primary uterine cervical LCNEC confirmed by the detection of HPV genome within the tumor. It is critical to recognize LCNEC of the uterine cervix even in the small biopsy specimen because it is a distinctive clinicopathological entity with highly aggressive behavior and unfavorable outcome.

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