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Molecular Profiling of Pheochromocytoma and Abdominal Paraganglioma Stratified by the PASS Algorithm Reveals Chromogranin B as Associated With Histologic Prediction of Malignant Behavior
Karolinska Univ Hosp, Sweden.
Karolinska Univ Hosp, Sweden.
Karolinska Univ Hosp, Sweden; Bushehr Univ Med Sci, Iran.
Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
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2019 (English)In: American Journal of Surgical Pathology, ISSN 0147-5185, E-ISSN 1532-0979, Vol. 43, no 3, p. 409-421Article in journal (Refereed) Published
Abstract [en]

Pheochromocytomas (PCCs) and abdominal paragangliomas (PGLs), collectively abbreviated PPGL, are believed to exhibit malignant potential-but only subsets of cases will display full-blown malignant properties. The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) algorithm is a proposed histologic system to detect potential for aggressive behavior, but little is known regarding the coupling to underlying molecular genetics. In this study, a total of 92 PPGLs, previously characterized for susceptibility gene status and mRNA expressional profiles, were histologically assessed using the PASS criteria. A total of 32/92 PPGLs (35%) exhibited a PASS score amp;gt;= 4, including all 8 cases with malignant behavior (7 with known metastases and 1 with extensively infiltrative local recurrence). Statistical analyzes between expressional data and clinical parameters as well as individual PASS criteria yielded significant associations to Chromogranin B (CHGB), BRCA2, HIST1H3B, BUB1B, and RET to name a few, and CHGB had the strongest correlation to both PASS and metastasis/local recurrence of all analyzed genes. Evident CHGB downregulation was observed in PPGLs with high PASS and overtly malignant behavior, and was also associated with shorter disease-related survival. This finding was validated using quantitative real-time polymerase chain reaction, in which CHGB expression correlated with both PASS and metastasis/local recurrence with consistent findings obtained in the TCGA cohort. Moreover, immunohistochemical analyses of subsets of tumors showed a correlation between high PASS scores and negative or weak CHGB protein expression. Patients with PPGLs obtaining high PASS scores postoperatively, also exhibited low preoperative plasma levels of CHGB. These data collectively point out CHGB as a possible preoperative and postoperative marker for PPGLs with potential for aggressive behavior.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS , 2019. Vol. 43, no 3, p. 409-421
Keywords [en]
pheochromocytoma; paraganglioma; malignancy; expressional profiling; CHGB
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-154987DOI: 10.1097/PAS.0000000000001190ISI: 000459205400014PubMedID: 30451732OAI: oai:DiVA.org:liu-154987DiVA, id: diva2:1297560
Note

Funding Agencies|Swedish Cancer Society; Cancer Research Funds of Radiumhemmet; Swedish Society for Medical Research; Stockholm County Council (ALF project); Karolinska Institutet

Available from: 2019-03-20 Created: 2019-03-20 Last updated: 2019-03-20

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Söderkvist, PeterGimm, Oliver
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Division of Cell BiologyFaculty of Medicine and Health SciencesDepartment of Clinical Pathology and Clinical GeneticsDivision of Surgery, Orthopedics and OncologyDepartment of Surgery in Linköping
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American Journal of Surgical Pathology
Cancer and Oncology

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