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Original Article
Loss of Progesterone Receptor Expression Is an Early Tumorigenesis Event Associated with Tumor Progression and Shorter Survival in Pancreatic Neuroendocrine Tumor Patients
Sung Joo Kim, Soyeon An, Jae Hoon Lee, Joo Young Kim, Ki-Byung Song, Dae Wook Hwang, Song Cheol Kim, Eunsil Yu, Seung-Mo Hong
J Pathol Transl Med. 2017;51(4):388-395.   Published online June 8, 2017
DOI: https://doi.org/10.4132/jptm.2017.03.19
  • 6,894 View
  • 136 Download
  • 17 Web of Science
  • 16 Crossref
AbstractAbstract PDF
Background
Pancreatic neuroendocrine tumors (PanNETs) are the second most common pancreatic neoplasms and there is no well-elucidated biomarker to stratify their detection and prognosis. Previous studies have reported that progesterone receptor (PR) expression status was associated with poorer survival in PanNET patients.
Methods
To validate previous studies, PR protein expression was assessed in 21 neuroendocrine microadenomas and 277 PanNETs and compared with clinicopathologic factors including patient survival.
Results
PR expression was gradually decreased from normal islets (49/49 cases, 100%) to neuroendocrine microadenoma (14/21, 66.6%) to PanNETs (60/277, 21.3%; p < .001). PanNETs with loss of PR expression were associated with increased tumor size (p < .001), World Health Organization grade (p = .001), pT classification (p < .001), perineural invasion (p = .028), lymph node metastasis (p = .004), activation of alternative lengthening of telomeres (p = .005), other peptide hormonal expression (p < .001) and ATRX/DAXX expression (p = .015). PanNET patients with loss of PR expression (5-year survival rate, 64.1%) had significantly poorer recurrence-free survival outcomes than those with intact PR expression (90%) by univariate (p = .012) but not multivariate analyses. Similarly, PanNET patients with PR expression loss (5-year survival rate, 76%) had significantly poorer overall survival by univariate (p = .015) but not multivariate analyses.
Conclusions
Loss of PR expression was noted in neuroendocrine microadenomas and was observed in the majority of PanNETs. This was associated with increased grade, tumor size, and advanced pT and pN classification; and was correlated with decreased patient survival time by univariate but not multivariate analyses. Loss of PR expression can provide additional information on shorter disease-free survival in PanNET patients.

Citations

Citations to this article as recorded by  
  • Sex Differences in the Survival of Patients with Neuroendocrine Neoplasms: A Comparative Study of Two National Databases
    Mohamed Mortagy, Marie Line El Asmar, Kandiah Chandrakumaran, John Ramage
    Cancers.2024; 16(13): 2376.     CrossRef
  • Association Between Female Sex and Better Survival in Gastroenteropancreatic Neuroendocrine Tumors
    Jeremy Chang, Mohammed O. Suraju, Catherine G. Tran, Carlos H.F. Chan, Po Hien Ear, James R. Howe, Scott K. Sherman
    Journal of Surgical Research.2024; 302: 53.     CrossRef
  • Incidence and Prognostic Implications of Lymphovascular Invasion in Node‐Negative Pancreatic Neuroendocrine Tumors: Results From the US Neuroendocrine Study Group
    Kota Sahara, Diamantis I. Tsilimigras, Yuki Homma, Jun Kawashima, Shishir K. Maithel, Flavio Rocha, Sharon Weber, Ryan Fields, Kamran Idrees, George A. Poultsides, Cliff Cho, Itaru Endo, Timothy M. Pawlik
    Journal of Surgical Oncology.2024;[Epub]     CrossRef
  • Venous invasion and lymphatic invasion are correlated with the postoperative prognosis of pancreatic neuroendocrine neoplasm
    Sho Kiritani, Junichi Arita, Yuichiro Mihara, Rihito Nagata, Akihiko Ichida, Yoshikuni Kawaguchi, Takeaki Ishizawa, Nobuhisa Akamatsu, Junichi Kaneko, Kiyoshi Hasegawa
    Surgery.2023; 173(2): 365.     CrossRef
  • Combined Infiltrative Macroscopic Growth Pattern and Infiltrative Microscopic Tumor Border Status Is a Novel Surrogate Marker of Poor Prognosis in Patients With Pancreatic Neuroendocrine Tumor
    Bokyung Ahn, Joo Young Kim, Seung-Mo Hong
    Archives of Pathology & Laboratory Medicine.2023; 147(1): 100.     CrossRef
  • HORMONET: a phase II trial of tamoxifen for estrogen/progesterone receptor-positive neuroendocrine tumors
    Milton J. Barros, Jonathan Strosberg, Taymeyah Al-Toubah, Victor Hugo F. de Jesus, Lais Durant, Celso A. Mello, Tiago C. Felismino, Louise De Brot, Rodrigo G. Taboada, Mauro D. Donadio, Rachel P. Riechelmann
    Therapeutic Advances in Medical Oncology.2023;[Epub]     CrossRef
  • Diagnostic and Prognostic Impact of Progesterone Receptor Immunohistochemistry: A Study Evaluating More Than 16,000 Tumors
    Florian Viehweger, Lisa-Marie Tinger, David Dum, Natalia Gorbokon, Anne Menz, Ria Uhlig, Franziska Büscheck, Andreas M. Luebke, Claudia Hube-Magg, Andrea Hinsch, Doris Höflmayer, Christoph Fraune, Patrick Lebok, Sören Weidemann, Maximilian Lennartz, Frank
    Analytical Cellular Pathology.2022; 2022: 1.     CrossRef
  • Prognostic Nomograms to Predict Overall Survival and Cancer-Specific Survival of Patients With Pancreatic Neuroendocrine Tumors
    Zuoli Song, Sumei Wang, Yujing Wu, Jinjuan Zhang, Shuye Liu
    Pancreas.2021; 50(3): 414.     CrossRef
  • Pancreatic High-Grade Neuroendocrine Neoplasms in the Korean Population: A Multicenter Study
    Haeryoung Kim, Soyeon An, Kyoungbun Lee, Sangjeong Ahn, Do Youn Park, Jo-Heon Kim, Dong-Wook Kang, Min-Ju Kim, Mee Soo Chang, Eun Sun Jung, Joon Mee Kim, Yoon Jung Choi, So-Young Jin, Hee Kyung Chang, Mee-Yon Cho, Yun Kyung Kang, Myunghee Kang, Soomin Ahn
    Cancer Research and Treatment.2020; 52(1): 263.     CrossRef
  • Systemic distribution of progesterone receptor subtypes in human tissues
    Teeranut Asavasupreechar, Ryoko Saito, Yasuhiro Miki, Dean P. Edwards, Viroj Boonyaratanakornkit, Hironobu Sasano
    The Journal of Steroid Biochemistry and Molecular Biology.2020; 199: 105599.     CrossRef
  • Progesteron receptor expression in insulin producing cells of neuroendocrine neoplasms
    Tomoyoshi Tachibana, Atsuko Kasajima, Takeshi Aoki, Tomoaki Tabata, Keely McNamara, Samaneh Yazdani, Sato Satoko, Fumiyoshi Fujishima, Fuyuhiko Motoi, Michiaki Unno, Hironobu Sasano
    The Journal of Steroid Biochemistry and Molecular Biology.2020; 201: 105694.     CrossRef
  • Prognostic and predictive factors on overall survival and surgical outcomes in pancreatic neuroendocrine tumors: recent advances and controversies
    Lingaku Lee, Tetsuhide Ito, Robert T Jensen
    Expert Review of Anticancer Therapy.2019; 19(12): 1029.     CrossRef
  • Immunohistochemistry, carcinomas of unknown primary, and incidence rates
    Edward B. Stelow, Hadi Yaziji
    Seminars in Diagnostic Pathology.2018; 35(2): 143.     CrossRef
  • Carbonic anhydrase 9 expression in well-differentiated pancreatic neuroendocrine neoplasms might be associated with aggressive behavior and poor survival
    Joo Young Kim, Sang Hwa Lee, Soyeon An, Sung Joo Kim, You-Na Sung, Ki-Byung Song, Dae Wook Hwang, Song Cheol Kim, Seung-Mo Hong
    Virchows Archiv.2018; 472(5): 739.     CrossRef
  • Prognostic value of progesterone receptor in solid pseudopapillary neoplasm of the pancreas: evaluation of a pooled case series
    Feiyang Wang, Zibo Meng, Shoukang Li, Yushun Zhang, Heshui Wu
    BMC Gastroenterology.2018;[Epub]     CrossRef
  • Estrogens modulate progesterone receptor expression and may contribute to progesterone-mediated apoptotic β-cell death
    Viviane Abreu Nunes
    Endocrinology&Metabolism International Journal.2018;[Epub]     CrossRef
Case Reports
Diffuse Large B-Cell Lymphoma Associated with Chronic Inflammation Manifested as a Soft Tissue Mass: Incidental Discovery on Histological Examination.
Sang Yun Ha, Yoon La Choi, Sung Joo Kim, Young Hye Ko
Korean J Pathol. 2011;45(4):417-422.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.4.417
  • 4,006 View
  • 35 Download
  • 5 Crossref
AbstractAbstract PDF
We report an extraordinary case of diffuse large B-cell lymphoma arising in a cystic necrotic mass in a 35-year-old man who presented with a soft tissue mass at the site of previous surgery. A benign mass was surgically removed 17 years ago, after which a cystic lesion gradually developed at the same site. The resected mass appeared as a thick-walled cyst filled with brown necrotic and hemorrhagic material. On microscopic examination, the cyst wall was primarily necrotic tissue with some aggregates of large atypical lymphoid cells. These atypical cells were diffusely positive for CD20 and showed a high proliferation index, Epstein-Barr virus positivity, and clonal rearrangement of the immunoglobulin gene. His present condition was diagnosed as Epstein-Barr virus-associated diffuse large B-cell lymphoma arising from chronic inflammation. It is important to be aware of the clinical manifestations and histological features of this rare disease in light of diagnosis and treatment.

Citations

Citations to this article as recorded by  
  • EBV-negative Fibrin-Associated Large B-Cell Lymphoma Arising in Thyroid Hyperplastic Nodule: Report of a Case and Literature Review
    Tin Wai Ho, Wah Cheuk, John K.C. Chan
    International Journal of Surgical Pathology.2023; 31(7): 1420.     CrossRef
  • Diffuse Large B Cell Lymphoma in a Prosthetic Aortic Graft
    David Bell, David Marshman
    Heart, Lung and Circulation.2017; 26(2): e4.     CrossRef
  • Fibrin-associated EBV-positive Large B-Cell Lymphoma
    Daniel F. Boyer, Penelope A. McKelvie, Laurence de Leval, Kerstin L. Edlefsen, Young-Hyeh Ko, Zachary A. Aberman, Alexandra E. Kovach, Aneal Masih, Ha T. Nishino, Lawrence M. Weiss, Alan K. Meeker, Valentina Nardi, Maryknoll Palisoc, Lina Shao, Stefania P
    American Journal of Surgical Pathology.2017; 41(3): 299.     CrossRef
  • Malignant Lymphoma Mimicking an Infection After Shoulder Surgery
    Jabari Ian Justin Martin, Jasmine Bauknight, Vincent Desiderio, Bahman Sadr
    Journal of the American Academy of Orthopaedic Surgeons.2017; 25(4): 314.     CrossRef
  • Current Concepts in Primary Effusion Lymphoma and Other Effusion-Based Lymphomas
    Yoonjung Kim, Chan Jeong Park, Jin Roh, Jooryung Huh
    Korean Journal of Pathology.2014; 48(2): 81.     CrossRef
Disseminated Systemic Candidiasis and Aspergillosis in a Liver Transplant Patient: An Autopsy Report.
Na Rae Kim, Dae Su Kim, Young Hyeh Ko, Sung Joo Kim
Korean J Pathol. 2002;36(5):348-352.
  • 1,687 View
  • 18 Download
AbstractAbstract PDF
Postoperative complications of liver transplantation include rejection, infection, hepatic vascular thrombus, and primary graft failure, etc. Among them, fungal infection shows nonspecific clinical symptoms and overlapping laboratory findings with variable etiologies causing post-transplant hepatic dysfunction. Therefore, early diagnosis of fungal infection is not easy. Here, we report an autopsy case of disseminated candidiasis and aspergillosis in a liver transplant patient. The case was at first misinterpreted as acute cellular rejection on biopsy because the histology of predominantly cellular infiltration, ductulitis and endothelialitis were similar to those of acute cellular rejection. On autopsy, the liver, lung and kidney showed multifocal hemorrhagic infarcts due to intra-arterial fungal emboli, which were composed mostly of candida species and a minor fraction of aspergillus. Fungal thrombi invading portal vein, intrahepatic arterioles with subsequent coagulation necrosis, venulitis and ductulitis were ascribed to the misdiagnosis on biopsies. It is unusual that systemic candidiasis, unlike aspergillosis, involves large arteries.
Giant Retroperitoneal Lipomatous Angiomyolipoma Simulating Liposarcoma: A Brief Case Report.
Dakeun Lee, Joungho Han, Sung Joo Kim, Dongil Choi
Korean J Pathol. 2007;41(6):406-408.
  • 1,509 View
  • 26 Download
AbstractAbstract PDF
Extrarenal retroperitoneal angiomyolipomas (AML) are extremely rare, therefore they may present a diagnostic challenge. In this paper, the authors describe a case of a huge retroperitoneal AML in a 49-year-old woman who presented with sudden abdominal pain. Computed tomography revealed the presence of a large, round, fatty mass in the retroperitoneal space, which was easily removed by surgery. The mass was well encapsulated and dark yellow on the cut surface. Microscopically, the tumor was exclusively composed of adipose tissue with frequent multivacuolated, lipoblast-like cells masquerading as well differentiated liposarcoma. In addition, there were many clear, epithelioid cells present, especially around the small blood vessels, which were reactive for HMB-45 and smooth muscle actin.

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