Journal of Pathology and Translational Medicine

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

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133 Download
14 Web of Science
13 Crossref

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

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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
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Carbonic anhydrase 9 expression in well-differentiated pancreatic neuroendocrine neoplasms might be associated with aggressive behavior and poor survival
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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 Study

Mammary-Type Myofibroblastoma: A Report of Two Cases: Soyeon An, Joon Seon Song, Soonchan Park, Jung Won Lee, Kyung-Ja Cho; J Pathol Transl Med. 2016;50(5):385-389. Published online June 6, 2016; DOI: https://doi.org/10.4132/jptm.2016.03.26

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135 Download
5 Web of Science
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Abstract PDF

Mammary-type myofibroblastoma (MFB) is a rare, benign spindle cell neoplasm occurring along the milkline, with extension from the mid-axilla to the medial groin. It is histologically and immunohistochemically identical to MFB of the breast and is part of a spectrum of lesions that includes spindle cell lipoma and cellular angiofibroma. Recently, we experienced two cases of mammary-type MFB involving male patients aged 30 and 58 years, respectively. The tumors were located in the right scrotal sac and in the right axilla. Wide excisions were performed. Microscopically, the masses were composed of haphazardly arranged, variably sized fascicles of bland spindle cells and were admixed with mature fat tissue. The spindle cells in both cases showed immunopositivity for desmin and CD34 and negativity for smooth muscle actin. Loss of retinoblastoma (RB)/13q14 loci is a characteristic genetic alteration of mammary-type MFB, and we identified loss of RB protein expression by immunohistochemical staining. We emphasize the importance of awareness of this rare neoplasm when a spindle cell neoplasm is accompanied by desmin immunopositivity. The second patient was alive without recurrence for 20 months, and the first patient had not been followed.

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Imaging features of mammary-type myofibroblastoma of soft tissue: a case series with literature review
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Original Article

Clinical and Prognostic Significances of Cytokeratin 19 and KIT Expression in Surgically Resectable Pancreatic Neuroendocrine Tumors: Eun-Mi Son, Joo Young Kim, Soyeon An, Ki-Byung Song, Song Cheol Kim, Eunsil Yu, Seung-Mo Hong; J Pathol Transl Med. 2015;49(1):30-36. Published online January 15, 2015; DOI: https://doi.org/10.4132/jptm.2014.10.23

10,388 View
83 Download
18 Web of Science
17 Crossref

Abstract PDF

Background
Pancreatic neuroendocrine tumors (PanNETs) are malignant endocrine neoplasms that present diverse clinical behaviors. Therefore, identification of biomarkers of PanNETs is important for stratification of the prognosis of PanNET patients. Recently, cytokeratin 19 (CK19) and KIT expression were reported to have prognostic significance in PanNET patients. Methods: To identify their prognostic significance, CK19 and KIT protein expression were assessed in 182 surgically resected PanNETs and compared with clinicopathologic factors. Results: Of 182 PanNETs cases, CK19 and KIT expression was noted in 97 (53.3%) and 16 (8.8%) cases, respectively. PanNET patients with CK19 expression had larger tumors (p=.006), higher World Health Organization (WHO) grade (p=.002) and pT classification (p<.001), increased distant metastasis (p=.004), and lymphovascular (p=.012) and perineural (p=.019) invasion. Similarly, those with KIT expression had larger tumors (p=.030), higher WHO grade (p=.001), advanced pT classification (p<.001), distant metastasis (p=.001), and lymphovascular invasion (p=.014). The 5-year survival rate for PanNET patients with KIT expression was significantly lower (62%) than that of patients without KIT expression (77%, p=.011), as determined by univariate but not by multivariate analyses. Conclusions: CK19 and KIT expression correlate with higher metastatic potential and advanced disease stage, and KIT expression is associated with worse survival in PanNET patients.

Citations

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Loss of Progesterone Receptor Expression Is an Early Tumorigenesis Event Associated with Tumor Progression and Shorter Survival in Pancreatic Neuroendocrine Tumor Patients
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