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Prerna Guleria
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P1.09 - Pathology (Not CME Accredited Session) (ID 941)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.09-11 - Immunohistochemical Assessment of BRCA1 Associated Protein-1 (BAP1) in Pulmonary Mucoepidermoid Carcinomas (ID 11322)
16:45 - 18:00 | Author(s): Prerna Guleria
- Abstract
Background
Primary pulmonary mucoepidermoid carcinomas (PMEC) are rare tumors that account for <1% of all lung carcinomas. They are presumed to originate from the minor salivary glands lining the tracheobronchial tree. PMEC are the most common malignant salivary gland tumors of tracheobronchial tree. Despite recent advances in diagnosis and treatment, there has not been much improvement in the outcome of patients with MECs, thus necessitating the identification of novel targeted therapeutic agents. Comprehensive genomic profiling has recently revealed genomic aberrations in BRCA1 associated protein-1 (BAP1) gene in a subset of their non-pulmonary salivary gland counterparts. We conducted this study to identify loss of BAP1 by immunohistochemistry (IHC) in a cohort of PMECs.
a9ded1e5ce5d75814730bb4caaf49419 Method
Cases of PMECs were retrieved from the departmental archives. Hematoxylin and eosin stained sections were reviewed. Immunohistochemistry for BAP1 was performed on formalin fixed paraffin-embedded tumor sections.
4c3880bb027f159e801041b1021e88e8 Result
Twenty-five PMEC cases were retrieved, out of which sufficient tumor tissue for IHC was available only in 15 PMECs. Thirteen (86.7%) tumors were tracheobronchial in location, while two (13.3%) were intraparenchymal. All were low grade MECs. On immunohistochemistry, BAP1 nuclear staining was retained in all cases (100%), irrespective of tumor location or grade.
8eea62084ca7e541d918e823422bd82e Conclusion
Identification of easily applicable techniques to detect BAP1 loss in PMECs is needed for therapeutic decisions. Using IHC, loss of BAP1 staining was not seen in any of our cases, suggesting either the extreme rarity of BAP1 loss in PMEC or insensitivity of BAP1 IHC to detect aberrations at genomic level. Analysis of aberrations in BAP1 gene by genomic approaches in PMECs may be done before excluding the possibility of BAP1 gene as a predictive biomarker for targeted therapies.
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P1.14 - Thymoma/Other Thoracic Malignancies (Not CME Accredited Session) (ID 946)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 3
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.14-12 - GTF2I Mutation in Thymomas: Indian and German Study (ID 14314)
16:45 - 18:00 | Author(s): Prerna Guleria
- Abstract
Background
Point mutation (L404H) of GTF2I gene on chromosome 7 has been identified in thymic epithelial tumors; most predominantly in A and AB histotypes and associated with good prognosis. The objective of this retrospective analysis was to assess the frequency of GTF2I mutation in Indian and German thymomas and correlate with WHO histotypes.
a9ded1e5ce5d75814730bb4caaf49419 Method
A cohort of Indian and German thymomas of different histotypes was retrieved from the archives. Clinicopathological details were obtained from case files. Hematoxylin-eosin stained slides were reviewed and histopathological subtypes along with Masaoka-Koga staging were determined. The available blocks were selected for DNA extraction. Tumors rich in cancer cells (>50%) were evaluated for GTF2I mutation using Sanger sequencing. Primer for Exon 15 of GTF2I gene was designed using NCBI and Primer 3 (v.0.4.0) software. Results were compiled and analysed.
4c3880bb027f159e801041b1021e88e8 Result
A total of 126 resection specimens were retrieved comprising 23 (18.2%) Type A, 30 (23.8%) Type AB 16 atypical A/AB (12.6%) and 30 (23.8%) Type B thymomas. Remaining 27 cases belonged to 18 thymic carcinomas, 2 sclerosing mediastinitis, 2 metaplastic thymomas, 1 thymolipoma, and 4 non-thymomatous lesions.
Out of a total of 69 A/AB thymomas, 53 (76.8%) were positive including 88% (22/25) Indian and 65.9 % (29/44) German cases. 26% (18/69) A/AB were negative. All Indian B histotypes (n=9) were negative, whereas 4 German B thymomas (4/21; 19%) were positive for GTF2I mutation. No mutations were found in non-thymomatous pathologies.
Among 34 Indian cases, there was equal gender distribution, median age was 48 years and 31 were in lower stage groups (Stage I and II). Clinical details and follow up available in 17 of 34 cases had a median follow up of 14 months and revealed presence of myasthenia gravis in 76.5% cases. Recurrence seen in 3 cases revealed high risk morphology (2 Type B histotypes and 1 atypical A) and one death of Type A was due to myasthenic crisis.
8eea62084ca7e541d918e823422bd82e Conclusion
The similarity of Indian and German (and previously published American) cohorts of A/B and type B thymomas in term of GTF2I mutation frequencies suggests a thymus-specific microenvironmental mutagenic mechanism and argues against a relevant impact of environmental or ethnic (germ line) factors. The unusually high prevalence of Myasthenia gravis among the Indian thymomas warrants further analysis to exclude referral bias.
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P1.14-13 - PD-L1 Immuno-Expression Assay in Thymomas: A Study from India (ID 11244)
16:45 - 18:00 | Author(s): Prerna Guleria
- Abstract
Background
Programmed death ligand 1 (PD-L1), an immune check point inhibitor, is known to be expressed in several malignancies and is being considered as a prognostic factor and a potential immunotherapeutic target. Recent development of anti-PD-1/L1 antibodies has demonstrated anticancer activity of these agents in various neoplasms. The aim of this study was to characterize PD-L1 expression in thymomas and to determine whether PD-L1 represents a therapeutic target in unresectable thymomas. A correlation with clinicopathological features and previously published studies in the literature was established.
a9ded1e5ce5d75814730bb4caaf49419 Method
Tissue microarrays were prepared from selected blocks of thymomas and immunohistochemistry (IHC) using SP263 clone of PD-L1 was performed. Cases were considered as PD-L1 positive or negative based on percentage of stained thymic epithelial cells; if these were <25 or >25 percent. Results were compared clinically and with previously published studies using Google and Pubmed search engines.
4c3880bb027f159e801041b1021e88e8 Result
Of 84 cases of thymoma, 69 (82.1%) revealed PD-L1 positivity in more than 25% cells. 94.23% of type B thymoma subtypes (B1/B2/B3) were PD-L1 positive (P<.001). There was no correlation of PD-L1 with age, gender, myasthenia gravis, the tumor size or stage of disease. So far, 9 studies of PD-L1 expression in thymic epithelial tumors are available in the literature; most of which showed PD-L1 expression in higher stage and B histotype however percentage positivity varied from 53.7% to over 90%.
8eea62084ca7e541d918e823422bd82e Conclusion
PD-L1 expression is frequent in type B (B1/B2/B3) thymomas. It can be easily evaluated by IHC even on small biopsies in unresectable cases. PD-L1 immunoassay will serve as a potential indicator for benefit from anti-PD-L1 antibody immunotherapy in thymomas thereby enabling improved clinical evaluation as well as prognostic stratification of patients.
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P1.14-14 - Histotyping of Indian Thymomas: A Comprehensive Clinicopathologic Study (ID 11242)
16:45 - 18:00 | Author(s): Prerna Guleria
- Abstract
Background
Thymomas are rare, but most common anterior mediastinal lesions. The WHO 2015 classification has defined criteria of classifying these into various subtypes. The histomorphologic spectrum of thymic epithelial tumors (TET) in Indian population has not been explored. We aimed to study the histomorphology of TETs in the Indian patients with clinico-pathological correlation.
a9ded1e5ce5d75814730bb4caaf49419 Method
It was a retrospective, tertiary referral centre, study. All cases of morphologically confirmed, surgically resected specimens and small biopsies diagnosed as TETs since 2009 were included. Clinical details and histology slides were reviewed using the Modified Masaoka-Koga staging system and WHO 2015 classification. Clinico-pathological correlation and survival analysis was done. Comparative review from other published Indian studies was performed.
4c3880bb027f159e801041b1021e88e8 Result
We identified 219 cases of TETs (138 resections and 81 biopsies). Most common histo-morphologic type was B2 and most frequent stage was I. Clinically, higher stage tumors were found mostly in men (P=.008) and these were type B thymomas (P=.01). Association of myasthenia gravis was prevalent in women (P=.02) and in lower stages (P=.04). Survival analysis revealed significant association between recurrence and tumor stage. Although thymic carcinoma was diagnosed on biopsy, no resectable case was identified.
8eea62084ca7e541d918e823422bd82e Conclusion
Literature lacks detailed histotyping of TETs from India. Indian thymomas are most commonly stage I tumors of B2 and AB histotypes. Resected thymic carcinomas are conspicuously absent in Indian cohort. We hope that broadening the spectrum of recognized pathologic manifestations of Indian thymomas will help global database for future studies.
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