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3. Recent Advances in the Classification of Gynecological Tract Tumors: Updates From the 5th Edition of the World Health Organization 'Blue Book'

Author

Parkash, Vinita, Aisagbonhi, Omonigho, Riddle, Nicole, Siddon, Alexa, Panse, Gauri, and Fadare, Oluwole

Subjects
Tumors, Papillomavirus infections, Public health, Health, World Health Organization
Abstract

Context.--The World Health Organization Classification of Tumours: Female Genital Tract Tumors, 5th edition, published in September 2020, comes 6 years after the 4th edition, and reflects the monumental leaps made in knowledge about the biology of gynecological tumors. Major changes include revised criteria for the assignment of the site of origin of ovarian and fallopian tube tumors, a revision in the classification of squamous and glandular lesions of the lower genital tract based on human papillomavirus association, and an entire chapter devoted to genetic tumor syndromes. This article highlights the changes in the 5th edition relative to the 4th edition, with a focus on areas of value to routine clinical practice. Objective.--To provide a comprehensive update on the World Health Organization classification of gynecological tumors, highlighting in particular updated diagnostic criteria and terminology. Data Sources.--The 4th and 5th editions of the World Health Organization Classification of Tumours. Conclusions.--The World Health Organization has made several changes in the 5th edition of the update on female genital tumors. Awareness of the changes is needed for pathologists' translation into contemporary practice. doi: 10.5858/arpa.2022-0166-RA, This review article summarizes key changes in the 5th edition of the World Health Organization (WHO) 'blue book' on tumors of the female genital tract (FGT) released in 2020. (1) [...]

Published
2023
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4. The Malignant Potential of Ovarian Steroid Cell Tumors Revisited: A Multi-institutional Clinicopathologic Analysis of 115 Cases

Author

Fadare, Oluwole, Fard, Elmira Vaziri, Bhargava, Rohit, Desouki, Mohamed Mokhtar, Hanley, Krisztina Z., Ip, Philip P.C., Li, Joshua J.X., Lu, Bingjian, Medeiros, Fabiola, Ng, Joshua Hoi Yan, Parkash, Vinita, Pinto, Andre, Quick, Charles M., Skala, Stephanie L., Tokuyama, Minami, Turashvili, Gulisa, Wei, Christina H., Xing, Deyin, Zheng, Wenxin, Soong, T. Rinda, and Howitt, Brooke E.

Published
2024
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7. Cancer-cell-secreted extracellular vesicles suppress insulin secretion through miR-122 to impair systemic glucose homeostasis and contribute to tumour growth

Author

Cao, Minghui, Isaac, Roi, Yan, Wei, Ruan, Xianhui, Jiang, Li, Wan, Yuhao, Wang, Jessica, Wang, Emily, Caron, Christine, Neben, Steven, Drygin, Denis, Pizzo, Donald P, Wu, Xiwei, Liu, Xuxiang, Chin, Andrew R, Fong, Miranda Y, Gao, Ziting, Guo, Kaizhu, Fadare, Oluwole, Schwab, Richard B, Yuan, Yuan, Yost, Susan E, Mortimer, Joanne, Zhong, Wenwan, Ying, Wei, Bui, Jack D, Sears, Dorothy D, Olefsky, Jerrold M, and Wang, Shizhen Emily

Subjects
Biochemistry and Cell Biology, Biological Sciences, Nutrition, Breast Cancer, Cancer, Diabetes, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Animals, Breast Neoplasms, Diabetes Mellitus, Type 2, Extracellular Vesicles, Female, Glucose, Homeostasis, Humans, Insulin, Insulin Secretion, Mice, MicroRNAs, Medical and Health Sciences, Developmental Biology, Biochemistry and cell biology
Abstract

Epidemiological studies demonstrate an association between breast cancer (BC) and systemic dysregulation of glucose metabolism. However, how BC influences glucose homeostasis remains unknown. We show that BC-derived extracellular vesicles (EVs) suppress pancreatic insulin secretion to impair glucose homeostasis. EV-encapsulated miR-122 targets PKM in β-cells to suppress glycolysis and ATP-dependent insulin exocytosis. Mice receiving high-miR-122 EVs or bearing BC tumours exhibit suppressed insulin secretion, enhanced endogenous glucose production, impaired glucose tolerance and fasting hyperglycaemia. These effects contribute to tumour growth and are abolished by inhibiting EV secretion or miR-122, restoring PKM in β-cells or supplementing insulin. Compared with non-cancer controls, patients with BC have higher levels of circulating EV-encapsulated miR-122 and fasting glucose concentrations but lower fasting insulin; miR-122 levels are positively associated with glucose and negatively associated with insulin. Therefore, EV-mediated impairment of whole-body glycaemic control may contribute to tumour progression and incidence of type 2 diabetes in some patients with BC.

Published
2022

8. A comprehensive immunohistochemical analysis of IMP2 and IMP3 in 542 cases of ovarian tumors

Author

Němejcová, Kristýna, Bártů, Michaela Kendall, Michálková, Romana, Drozenová, Jana, Fabian, Pavel, Fadare, Oluwole, Hausnerová, Jitka, Laco, Jan, Matěj, Radoslav, Méhes, Gábor, Singh, Naveena, Stolnicu, Simona, Škapa, Petr, Švajdler, Marián, Stružinská, Ivana, Cibula, David, Kocian, Roman, Lax, Sigurd F., McCluggage, W. Glenn, and Dundr, Pavel

Published
2023
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9. Syndrome of inappropriate antidiuretic hormone secretion associated with an ovarian immature teratoma: A case report and review of the literature

Author

Hom-Tedla, Marianne, Brodsky, Allison, Fadare, Oluwole, Meriwether, Claire, and McHale, Michael

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Ovarian Cancer, Cancer, Rare Diseases, Hyponatremia, Immature teratoma, Surgery
Abstract

•SIADH can be associated with an ovarian immature teratoma.•Medical management of SIADH improved but did not resolve the hyponatremia.•Complete resolution of the hyponatremia was only obtained after surgical debulking.

Published
2022

12. Presence and extent of lymphovascular invasion in surgical stage I squamous cell carcinoma of the cervix: a comprehensive, international, multicentre, retrospective clinicopathological study

Author

Stolnicu, Simona, Allison, Douglas, Tessier-Cloutier, Basile, Momeni-Boroujeni, Amir, Hoang, Lien, Ieni, Antonio, Felix, Ana, Terinte, Cristina, Pesci, Anna, Mateoiu, Claudia, Hodgson, Anjelica, Guerra, Esther, de Brot, Louise, Lastra, Ricardo R., Kiyokawa, Takako, Ali-Fehmi, Rouba, Kheil, Mira, Dundr, Pavel, Roma, Andres, Fadare, Oluwole, Turashvili, Gulisa, Oliva, Esther, Devins, Kyle M., Baiocchi, Glauco, Cibula, David, and Soslow, Robert A.

Published
2024
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15. Microsatellite instability in non-endometrioid ovarian epithelial tumors: a study of 400 cases comparing immunohistochemistry, PCR, and NGS based testing with mutation status of MMR genes

Author

Hájková, Nikola, Bártů, Michaela Kendall, Cibula, David, Drozenová, Jana, Fabian, Pavel, Fadare, Oluwole, Frühauf, Filip, Hausnerová, Jitka, Hojný, Jan, Krkavcová, Eva, Laco, Jan, Lax, Sigurd F., Matěj, Radoslav, Méhes, Gábor, Michálková, Romana, Němejcová, Kristýna, Singh, Naveena, Stolnicu, Simona, Švajdler, Marián, Zima, Tomáš, McCluggage, Wilson Glenn, Stružinská, Ivana, and Dundr, Pavel

Published
2023
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16. Refined criteria for p53 expression in ovarian mucinous tumours are highly concordant with TP53 mutation status, but p53 expression/TP53 status lack prognostic significance

Author

Dundr, Pavel, Hájková, Nikola, Kendall Bártů, Michaela, Cibula, David, Drozenová, Jana, Fabian, Pavel, Fadare, Oluwole, Frühauf, Filip, Hausnerová, Jitka, Hojný, Jan, Laco, Jan, Lax, Sigurd F., Matěj, Radoslav, Méhes, Gábor, Michálková, Romana, Němejcová, Kristýna, Singh, Naveena, Stolnicu, Simona, Švajdler, Marián, Zima, Tomáš, McCluggage, W. Glenn, and Stružinská, Ivana

Published
2023
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19. The cytokeratin 17 expression in primary ovarian tumors has diagnostic but not prognostic significance

Author

Dundr, Pavel, Bazalová, Barbora, Bártů, Michaela, Bosse, Tjalling, Drozenová, Jana, Fabian, Pavel, Fadare, Oluwole, Hausnerová, Jitka, Jakša, Radek, Laco, Jan, Lax, Sigurd F., Matěj, Radoslav, McCluggage, W. Glenn, Méhes, Gábor, Michálková, Romana, Němejcová, Kristýna, Singh, Naveena, Stolnicu, Simona, Škapa, Petr, Švajdler, Marián, and Stružinská, Ivana

Published
2022
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20. Primary Mucinous Tumors of the Ovary: An Interobserver Reproducibility and Detailed Molecular Study Reveals Significant Overlap Between Diagnostic Categories

Author

Dundr, Pavel, Bártů, Michaela, Bosse, Tjalling, Bui, Quang Hiep, Cibula, David, Drozenová, Jana, Fabian, Pavel, Fadare, Oluwole, Hausnerová, Jitka, Hojný, Jan, Hájková, Nikola, Jakša, Radek, Laco, Jan, Lax, Sigurd F., Matěj, Radoslav, Méhes, Gábor, Michálková, Romana, Šafanda, Adam, Němejcová, Kristýna, Singh, Naveena, Stolnicu, Simona, Švajdler, Marián, Zima, Tomáš, Stružinská, Ivana, and McCluggage, W. Glenn

Published
2023
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21. Multi-institutional Assessment of Pathologist Scoring HER2 Immunohistochemistry

Author

Robbins, Charles J., Fernandez, Aileen I., Han, Gang, Wong, Serena, Harigopal, Malini, Podoll, Mirna, Singh, Kamaljeet, Ly, Amy, Kuba, M. Gabriela, Wen, Hannah, Sanders, Mary Ann, Brock, Jane, Wei, Shi, Fadare, Oluwole, Hanley, Krisztina, Jorns, Julie, Snir, Olivia L., Yoon, Esther, Rabe, Kim, Soong, T. Rinda, Reisenbichler, Emily S., and Rimm, David L.

Published
2023
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22. Ensuring remote diagnostics for pathologists: an open letter to the US Congress

Author

Lennerz, Jochen K., Pantanowitz, Liron, Amin, Mitual B., Eltoum, Isam-Eldin, Hameed, Meera R., Kalof, Alexana N., Khanafshar, Elham, Kunju, Lakshmi P., Lazenby, Audrey J., Montone, Kathleen T., Otis, Christopher N., Reid, Michelle D., Staats, Paul N., Whitney-Miller, Christa L., Abendroth, Catherine S., Aron, Manju, Birdsong, George G., Bleiweiss, Ira J., Bronner, Mary P., Chapman, Jennifer, Cipriani, Nicole A., de la Roza, Gustavo, Esposito, Michael J., Fadare, Oluwole, Ferrer, Karen, Fletcher, Christopher D., Frishberg, David P., Garcia, Fernando U., Geldenhuys, Laurette, Gill, Ryan M., Gui, Dorina, Halat, Shams, Hameed, Omar, Hornick, Jason L., Huber, Aaron R., Jain, Dhanpat, Jhala, Nirag, Jorda, Merce, Jorns, Julie M., Kaplan, Jeffrey, Khalifa, Mahmoud A., Khan, Ashraf, Kim, Grace E., Lee, Eun Y., LiVolsi, Virginia A., Longacre, Teri, Magi-Galluzzi, Cristina, McCall, Shannon J., McPhaul, Laron, Mehta, Vikas, Merzianu, Mihai, Miller, Stacey B., Molberg, Kyle H., Moreira, Andre L., Naini, Bita V., Nosé, Vania, O’Toole, Kathleen, Picken, Maria, Prieto, Victor G., Pullman, James M., Quick, Charles M., Reynolds, Jordan P., Rosenberg, Andrew E., Schnitt, Stuart J., Schwartz, Mary R., Sekosan, Marin, Smith, Michael T., Sohani, Aliyah, Stowman, Anne, Vanguri, Vijay K., Wang, Beverly, Watts, John C., Wei, Shi, Whitney, Kathleen, Younes, Mamoun, Zee, Sui, and Bracamonte, Erika R.

Published
2022
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24. Endometrial Polyp-Like Lesions Arising From Adenomyosis: Report of 5 Cases.

Author

St. Louis, Hailee, Renshaw, Idris L., and Fadare, Oluwole

Subjects
ENDOMETRIAL hyperplasia, SENTINEL lymph nodes, HYSTERO-oophorectomy, UTERINE prolapse, ENDOMETRIOSIS, ENDOMETRIUM
Abstract

This article discusses a study on endometrial polyp-like lesions arising from adenomyosis. Adenomyosis is a common gynecologic disease characterized by the presence of endometrial glands and stroma within the myometrium. The study presents 5 cases of this distinctive lesion and expands their pathologic spectrum. The patients ranged in age from 47 to 75 years and their uteri were resected for various indications. The study describes two patterns of endometrial polyp-like lesions and discusses their histological features. The article concludes by stating that these cases further expand the understanding of endometrial polyp-like lesions arising from adenomyosis. [Extracted from the article]

Published
2024
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25. Comparing loop electrosurgical procedure pathology results in the inpatient and outpatient setting.

Author

Brodsky, Allison L., Mathers, Hannah, Pebley, Nicole, Jacobs, Marni B., Fadare, Oluwole, and Eskander, Ramez N.

Abstract

Loop electrosurgical excision procedures (LEEPs) provide diagnostic information and may be therapeutic. There is limited evidence comparing LEEP outcomes as they relate to treatment setting. We sought to evaluate specimen outcomes of inpatient versus outpatient LEEPs. All patients who underwent LEEP over eight years at a single institution were identified retrospectively. Chart review was conducted to extract data. We analyzed 868 LEEP specimens; 86.4% from the outpatient and 13.6% from the inpatient setting. There was no significant difference in the rates of positive margins or thermal artifact. Fragmentation of the specimen was noted in 39% of inpatient LEEPs compared to 26.1% of outpatient LEEPs (p = 0.14). The median depth of specimen was 8 millimeters in both groups. These results suggest that outpatient LEEP may be equally effective in the management of cervical intraepithelial neoplasia with potential cost and patient safety implications. [ABSTRACT FROM AUTHOR]

Published
2024
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26. Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients

Author

Adamson, Kathi, Albain, Kathy S., Asare, Adam L., Asare, Smita M., Balassanian, Ron, Beckwith, Heather, Berry, Scott M., Berry, Donald A., Boughey, Judy C., Buxton, Meredith B., Chen, Yunn-Yi, Chen, Beiyun, Chien, A. Jo, Chui, Stephen Y., Clark, Amy S., Clennell, Julia L., Datnow, Brian, DeMichele, Angela M., Duan, Xiuzhen, Edmiston, Kirsten K., Elias, Anthony D., Ellis, Erin D., Esserman, Laura L., Euhus, David M., Fadare, Oluwole, Fan, Fang, Feldman, Michael D, Forero-Torres, Andres, Haley, Barbara B., Han, Hyo S., Harada, Shuko, Haugen, Patricia, Helsten, Teresa, Hirst, Gillian L., Hylton, Nola M., Isaacs, Claudine, Kemmer, Kathleen, Khan, Qamar J., Khazai, Laila, Klein, Molly E., Krings, Gregor, Lang, Julie E., LeBeau, Lauren G., Leyland-Jones, Brian, Liu, Minetta C., Lo, Shelly, Lu, Janice, Magliocco, Anthony, Matthews, Jeffrey B., Melisko, Michelle E., Mhawech-Fauceglia, Paulette, Moulder, Stacy L., Murthy, Rashmi K., Nanda, Rita, Northfelt, Donald W., Ocal, Idris T., Olopade, Olufunmilayo, Pambuccian, Stefan, Paoloni, Melissa, Park, John W., Parker, Barbara A., Perlmutter, Jane, Peterson, Garry, Pusztai, Lajos, Rendi, Mara, Rugo, Hope S., Sahoo, Sunati, Sams, Sharon, Sanil, Ashish, Sattar, Husain, Schwab, Richard B., Singhrao, Ruby, Steeg, Katherine, Stringer-Reasor, Erica, Symmans, W. Fraser, Tawfik, Ossama, Tripathy, Debasish, Troxell, Megan L., van't Veer, Laura J., Venters, Sara J., Vinh, Tuyethoa, Viscusi, Rebecca K., Wallace, Anne M., Wei, Shi, Wilson, Amy, Yau, Christina, Yee, Douglas, Zeck, Jay C., Osdoit, Marie, van der Noordaa, Marieke, Shad, Sonal, Wei, Jane, de Croze, Diane, Hamy, Anne-Sophie, Laé, Marick, Reyal, Fabien, Sonke, Gabe S, Steenbruggen, Tessa G, van Seijen, Maartje, Wesseling, Jelle, Martín, Miguel, del Monte-Millán, Maria, López-Tarruella, Sara, Boughey, Judy C, Goetz, Matthew P, Hoskin, Tanya, Gould, Rebekah, Valero, Vicente, Edge, Stephen B, Abraham, Jean E, Bartlett, John M S, Caldas, Carlos, Dunn, Janet, Earl, Helena, Hayward, Larry, Hiller, Louise, Provenzano, Elena, Sammut, Stephen-John, Thomas, Jeremy S, Cameron, David, Graham, Ashley, Hall, Peter, Mackintosh, Lorna, Godwin, Andrew K, Schwensen, Kelsey, Sharma, Priyanka, DeMichele, Angela M, Cole, Kimberly, Kim, Mi-Ok, van 't Veer, Laura J, Esserman, Laura J, and Symmans, W Fraser

Published
2022
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27. Cancer-cell-secreted exosomal miR-105 promotes tumour growth through the MYC-dependent metabolic reprogramming of stromal cells

Author

Yan, Wei, Wu, Xiwei, Zhou, Weiying, Fong, Miranda Y, Cao, Minghui, Liu, Juan, Liu, Xiaojing, Chen, Chih-Hong, Fadare, Oluwole, Pizzo, Donald P, Wu, Jiawen, Liu, Liang, Liu, Xuxiang, Chin, Andrew R, Ren, Xiubao, Chen, Yuan, Locasale, Jason W, and Wang, Shizhen Emily

Subjects
Biochemistry and Cell Biology, Biological Sciences, Breast Cancer, Cancer, Nutrition, Genetics, Biotechnology, 2.1 Biological and endogenous factors, Aetiology, Animals, Breast Neoplasms, Cancer-Associated Fibroblasts, Cell Line, Tumor, Cell Proliferation, Cellular Reprogramming, Energy Metabolism, Exosomes, Female, Gene Expression Regulation, Neoplastic, Humans, Mice, Mice, Inbred NOD, Mice, SCID, MicroRNAs, NIH 3T3 Cells, Paracrine Communication, Proto-Oncogene Proteins c-myc, Signal Transduction, Stromal Cells, Time Factors, Tumor Burden, Tumor Cells, Cultured, Tumor Microenvironment, Medical and Health Sciences, Developmental Biology, Biochemistry and cell biology
Abstract

Cancer and other cells residing in the same niche engage various modes of interactions to synchronize and buffer the negative effects of environmental changes. Extracellular microRNAs (miRNAs) have recently been implicated in the intercellular crosstalk. Here we show a mechanistic model involving breast-cancer-secreted, extracellular-vesicle-encapsulated miR-105, which is induced by the oncoprotein MYC in cancer cells and, in turn, activates MYC signalling in cancer-associated fibroblasts (CAFs) to induce a metabolic program. This results in the capacity of CAFs to display different metabolic features in response to changes in the metabolic environment. When nutrients are sufficient, miR-105-reprogrammed CAFs enhance glucose and glutamine metabolism to fuel adjacent cancer cells. When nutrient levels are low and metabolic by-products accumulate, these CAFs detoxify metabolic wastes, including lactic acid and ammonium, by converting them into energy-rich metabolites. Thus, the miR-105-mediated metabolic reprogramming of stromal cells contributes to sustained tumour growth by conditioning the shared metabolic environment.

Published
2018

41. Endometrial Precancers

Author

Quick, Charles Matthew, Fadare, Oluwole, Zheng, Wenxin, Zheng, Wenxin, editor, Fadare, Oluwole, editor, Quick, Charles Matthew, editor, Shen, Danhua, editor, and Guo, Donghui, editor

Published
2019
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42. Endometrial Carcinogenesis

Author

Zheng, Wenxin, Fadare, Oluwole, Quick, Charles Matthew, Zheng, Wenxin, editor, Fadare, Oluwole, editor, Quick, Charles Matthew, editor, Shen, Danhua, editor, and Guo, Donghui, editor

Published
2019
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45. Shed urinary ALCAM is an independent prognostic biomarker of three-year overall survival after cystectomy in patients with bladder cancer

Author

Egloff, Shanna A Arnold, Du, Liping, Loomans, Holli A, Starchenko, Alina, Su, Pei-Fang, Ketova, Tatiana, Knoll, Paul B, Wang, Jifeng, Haddad, Ahmed Q, Fadare, Oluwole, Cates, Justin M, Lotan, Yair, Shyr, Yu, Clark, Peter E, and Zijlstra, Andries

Subjects
Cancer, Urologic Diseases, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Good Health and Well Being, Activated-Leukocyte Cell Adhesion Molecule, Aged, Biomarkers, Tumor, Cohort Studies, Computational Biology, Cystectomy, Databases, Genetic, Female, Gene Expression, Gene Expression Profiling, Humans, Male, Middle Aged, Neoplasm Staging, Prognosis, Proportional Hazards Models, Reproducibility of Results, Urinary Bladder Neoplasms, ALCAM, bladder cancer, transitional cell carcinoma, urothelial cell carcinoma, metastasis, Oncology and Carcinogenesis
Abstract

Proteins involved in tumor cell migration can potentially serve as markers of invasive disease. Activated Leukocyte Cell Adhesion Molecule (ALCAM) promotes adhesion, while shedding of its extracellular domain is associated with migration. We hypothesized that shed ALCAM in biofluids could be predictive of progressive disease. ALCAM expression in tumor (n = 198) and shedding in biofluids (n = 120) were measured in two separate VUMC bladder cancer cystectomy cohorts by immunofluorescence and enzyme-linked immunosorbent assay, respectively. The primary outcome measure was accuracy of predicting 3-year overall survival (OS) with shed ALCAM compared to standard clinical indicators alone, assessed by multivariable Cox regression and concordance-indices. Validation was performed by internal bootstrap, a cohort from a second institution (n = 64), and treatment of missing data with multiple-imputation. While ALCAM mRNA expression was unchanged, histological detection of ALCAM decreased with increasing stage (P = 0.004). Importantly, urine ALCAM was elevated 17.0-fold (P < 0.0001) above non-cancer controls, correlated positively with tumor stage (P = 0.018), was an independent predictor of OS after adjusting for age, tumor stage, lymph-node status, and hematuria (HR, 1.46; 95% CI, 1.03-2.06; P = 0.002), and improved prediction of OS by 3.3% (concordance-index, 78.5% vs. 75.2%). Urine ALCAM remained an independent predictor of OS after accounting for treatment with Bacillus Calmette-Guerin, carcinoma in situ, lymph-node dissection, lymphovascular invasion, urine creatinine, and adjuvant chemotherapy (HR, 1.10; 95% CI, 1.02-1.19; P = 0.011). In conclusion, shed ALCAM may be a novel prognostic biomarker in bladder cancer, although prospective validation studies are warranted. These findings demonstrate that markers reporting on cell motility can act as prognostic indicators.

Published
2017

46. Shed urinary ALCAM is an independent prognostic biomarker of three-year overall survival after cystectomy in patients with bladder cancer.

Author

Arnold Egloff, Shanna A, Du, Liping, Loomans, Holli A, Starchenko, Alina, Su, Pei-Fang, Ketova, Tatiana, Knoll, Paul B, Wang, Jifeng, Haddad, Ahmed Q, Fadare, Oluwole, Cates, Justin M, Lotan, Yair, Shyr, Yu, Clark, Peter E, and Zijlstra, Andries

Subjects
Humans, Activated-Leukocyte Cell Adhesion Molecule, Neoplasm Staging, Prognosis, Cystectomy, Proportional Hazards Models, Cohort Studies, Reproducibility of Results, Gene Expression Profiling, Computational Biology, Gene Expression, Databases, Genetic, Aged, Middle Aged, Female, Male, Urinary Bladder Neoplasms, Biomarkers, Tumor, ALCAM, bladder cancer, metastasis, transitional cell carcinoma, urothelial cell carcinoma, Biomarkers, Tumor, Databases, Genetic, Oncology and Carcinogenesis
Abstract

Proteins involved in tumor cell migration can potentially serve as markers of invasive disease. Activated Leukocyte Cell Adhesion Molecule (ALCAM) promotes adhesion, while shedding of its extracellular domain is associated with migration. We hypothesized that shed ALCAM in biofluids could be predictive of progressive disease. ALCAM expression in tumor (n = 198) and shedding in biofluids (n = 120) were measured in two separate VUMC bladder cancer cystectomy cohorts by immunofluorescence and enzyme-linked immunosorbent assay, respectively. The primary outcome measure was accuracy of predicting 3-year overall survival (OS) with shed ALCAM compared to standard clinical indicators alone, assessed by multivariable Cox regression and concordance-indices. Validation was performed by internal bootstrap, a cohort from a second institution (n = 64), and treatment of missing data with multiple-imputation. While ALCAM mRNA expression was unchanged, histological detection of ALCAM decreased with increasing stage (P = 0.004). Importantly, urine ALCAM was elevated 17.0-fold (P < 0.0001) above non-cancer controls, correlated positively with tumor stage (P = 0.018), was an independent predictor of OS after adjusting for age, tumor stage, lymph-node status, and hematuria (HR, 1.46; 95% CI, 1.03-2.06; P = 0.002), and improved prediction of OS by 3.3% (concordance-index, 78.5% vs. 75.2%). Urine ALCAM remained an independent predictor of OS after accounting for treatment with Bacillus Calmette-Guerin, carcinoma in situ, lymph-node dissection, lymphovascular invasion, urine creatinine, and adjuvant chemotherapy (HR, 1.10; 95% CI, 1.02-1.19; P = 0.011). In conclusion, shed ALCAM may be a novel prognostic biomarker in bladder cancer, although prospective validation studies are warranted. These findings demonstrate that markers reporting on cell motility can act as prognostic indicators.

Published
2017

49. Prospective multi-institutional evaluation of pathologist assessment of PD-L1 assays for patient selection in triple negative breast cancer

Author

Reisenbichler, Emily S., Han, Gang, Bellizzi, Andrew, Bossuyt, Veerle, Brock, Jane, Cole, Kimberly, Fadare, Oluwole, Hameed, Omar, Hanley, Krisztina, Harrison, Beth T., Kuba, M. Gabriela, Ly, Amy, Miller, Dylan, Podoll, Mirna, Roden, Anja C., Singh, Kamaljeet, Sanders, Mary Ann, Wei, Shi, Wen, Hannah, Pelekanou, Vasiliki, Yaghoobi, Vesal, Ahmed, Fahad, Pusztai, Lajos, and Rimm, David L.

Published
2020
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