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Deep learning-based classifier for carcinoma of unknown primary using methylation quantitative trait loci

Walker, Adam; Fang, Camila S; Schroff, Chanel; Serrano, Jonathan; Vasudevaraja, Varshini; Yang, Yiying; Belakhoua, Sarra; Faustin, Arline; William, Christopher M; Zagzag, David; Chiang, Sarah; Acosta, Andres Martin; Movahed-Ezazi, Misha; Park, Kyung; Moreira, Andre L; Darvishian, Farbod; Galbraith, Kristyn; Snuderl, Matija
Cancer of unknown primary (CUP) constitutes between 2% and 5% of human malignancies and is among the most common causes of cancer death in the United States. Brain metastases are often the first clinical presentation of CUP; despite extensive pathological and imaging studies, 20%-45% of CUP are never assigned a primary site. DNA methylation array profiling is a reliable method for tumor classification but tumor-type-specific classifier development requires many reference samples. This is difficult to accomplish for CUP as many cases are never assigned a specific diagnosis. Recent studies identified subsets of methylation quantitative trait loci (mQTLs) unique to specific organs, which could help increase classifier accuracy while requiring fewer samples. We performed a retrospective genome-wide methylation analysis of 759 carcinoma samples from formalin-fixed paraffin-embedded tissue samples using Illumina EPIC array. Utilizing mQTL specific for breast, lung, ovarian/gynecologic, colon, kidney, or testis (BLOCKT) (185k total probes), we developed a deep learning-based methylation classifier that achieved 93.12% average accuracy and 93.04% average F1-score across a 10-fold validation for BLOCKT organs. Our findings indicate that our organ-based DNA methylation classifier can assist pathologists in identifying the site of origin, providing oncologists insight on a diagnosis to administer appropriate therapy, improving patient outcomes.
PMCID:11747144
PMID: 39607989
ISSN: 1554-6578
CID: 5778232

Correlation of Programmed Death-Ligand 1 Expression With Lung Adenocarcinoma Histologic and Molecular Subgroups in Primary and Metastatic Sites

Argyropoulos, Kimon; Basu, Atreyee; Park, Kyung; Zhou, Fang; Moreira, Andre L; Narula, Navneet
Programmed death-ligand 1 (PD-L1) expression in terms of the tumor proportion score (TPS) is the main predictive biomarker approved for immunotherapy against lung nonsmall cell carcinoma. Although some studies have explored the associations between histology and PD-L1 expression in pulmonary adenocarcinoma, they have been limited in sample size and/or extent of examined histologic variables, which may have resulted in conflicting information. In this observational retrospective study, we identified primary and metastatic lung adenocarcinoma cases in the span of 5 years and tabulated the detailed histopathologic features, including pathological stage, tumor growth pattern, tumor grade, lymphovascular and pleural invasion, molecular alterations, and the associated PD-L1 expression for each case. Statistical analyses were performed to detect associations between PD-L1 and these features. Among 1658 cases, 643 were primary tumor resections, 751 were primary tumor biopsies, and 264 were metastatic site biopsies or resections. Higher TPS significantly correlated with high-grade growth patterns, grade 3 tumors, higher T and N stage, presence of lymphovascular invasion, and presence of MET and TP53 alterations, whereas lower TPS correlated with lower-grade tumors and presence of EGFR alterations. There was no difference in PD-L1 expression in matched primary and metastases, although higher TPS was observed in metastatic tumors due to the presence of high-grade patterns in these specimens. TPS showed a strong association with a histologic pattern. Higher-grade tumors had higher TPS, which is also associated with more aggressive histologic features. Tumor grade should be kept in mind when selecting cases and blocks for PD-L1 testing.
PMID: 37307880
ISSN: 1530-0285
CID: 5725082

Utility of Urine Cytology Specimens for Molecular Profiling in Detection of High-Grade Urothelial Carcinoma [Meeting Abstract]

Chen, Fei; Belovarac, Brendan; Shen, Guomiao; Feng, Xiaojun; Jour, George; Sun, Wei; Snuderl, Matija; Simsir, Aylin; Park, Kyung
ISI:000990969800304
ISSN: 0023-6837
CID: 5525442

Genomic Profiling of Metastatic Tumors in Pleural Effusion Specimens: Comparison of Fresh Supernatant, Fresh Cell Pellet, and Cell Block Material for Testing [Meeting Abstract]

Chen, Fei; Belovarac, Brendan; Shen, Guomiao; Feng, Xiaojun; Brandler, Tamar; Jour, George; Sun, Wei; Snuderl, Matija; Park, Kyung; Simsir, Aylin
ISI:000990969800303
ISSN: 0023-6837
CID: 5525432

Malignant lymphoma of the lower urinary tract: A single institutional experience

Hoskoppal, Deepthi; Ren, Qinghu; Huang, Hongying; Park, Kyung; Deng, Fang-Ming
Lymphoma of the urinary tract is relatively rare and comprises of < 5% of all primary extra nodal lymphoma. Diagnoses of these lesions at anearly stage is important as they can disseminate or transform into high grade lesion if there is a delay in the diagnoses. There are only few case series and case reports on the malignant lymphoma of the urinary tract. The aim of this study was to characterize lymphoma involving the urinary bladder and prostate. We retrospectively reviewed the clinical data and histologic findings of the malignant lymphoma involving urinary bladder and prostate at our institution. Lymphoma involving the lower urinary tract clinically presented with lower urinary tract symptoms and usually with concurrent associated urinary bladder cancer or prostatic cancer in our series. Lymphoma should be included in the differential diagnoses especially in patients with prior history of lymphoid disorders. There should be a high index of suspicion when there is any atypical lymphoid infiltrate in routine urinary bladder and prostate surgical specimens.
PMID: 35526304
ISSN: 1618-0631
CID: 5213972

Methylation Profiling of Papillary Renal Neoplasm with Reverse Polarity [Meeting Abstract]

Park, Kyung; Serrano, Jonathan; Tran, Ivy; Feng, Xiaojun; Chen, Fei; Vasudevaraja, Varshini; Mirsadraei, Leili; Snuderl, Matija; Deng, Fang-Ming
ISI:000770361801237
ISSN: 0893-3952
CID: 5208642

Methylation Profiling of Papillary Renal Neoplasm with Reverse Polarity [Meeting Abstract]

Park, Kyung; Serrano, Jonathan; Tran, Ivy; Feng, Xiaojun; Chen, Fei; Vasudevaraja, Varshini; Mirsadraei, Leili; Snuderl, Matija; Deng, Fang-Ming
ISI:000770360201237
ISSN: 0023-6837
CID: 5208632

Tubulopapillary Carcinoma of the Breast: A Distinct Morphologic Entity with Molecular and Immunohistochemical Analysis [Meeting Abstract]

Salama, Abeer; Schwartz, Christopher; Zhu, Kelsey; Vasudevaraja, Varshini; Serrano, Jonathan; Jour, George; Park, Kyung; Snuderl, Matija; Cotzia, Paolo; Darvishian, Farbod
ISI:000770360200172
ISSN: 0023-6837
CID: 5243152

Comparison of Fresh Cell Pellets and Cell Blocks for Genomic Profiling of Advanced Cancers in Pleural Effusion Specimens: Promising Preliminary Results from a Validation Study [Meeting Abstract]

Chen, Fei; Kim, Christine; Shen, Guomiao; Feng, Xiaojun; Jour, George; Cotzia, Paolo; Brandler, Tamar; Sun, Wei; Snuderl, Matija; Simsir, Aylin; Park, Kyung
ISI:000770360200230
ISSN: 0023-6837
CID: 5243162

Comparison of Fresh Cell Pellets and Cell Blocks for Genomic Profiling of Advanced Cancers in Pleural Effusion Specimens: Promising Preliminary Results from a Validation Study [Meeting Abstract]

Chen, Fei; Kim, Christine; Shen, Guomiao; Feng, Xiaojun; Jour, George; Cotzia, Paolo; Brandler, Tamar; Sun, Wei; Snuderl, Matija; Simsir, Aylin; Park, Kyung
ISI:000770361800231
ISSN: 0893-3952
CID: 5243292