cyclin-d1 and Neoplasms--Cystic--Mucinous--and-Serous

About 8384 cases of solid pseudopapillary neoplasms (SPN) of pancreas have been published in English literature, from 1933 to 2018. This is a low-grade tumor that usually occurs in children but is rare in adults and, in exceptional cases, can show extrapancreatic localization. In this paper we present 2 unusual cases of SPNs, 1 with retroperitoneal location (case 1) and 1 that was firstly diagnosed as a G1 neuroendocrine tumor (NET) and showed hepatic metastases after 13 years (case 2).. No symptoms in first case. The tumor was incidentally diagnosed, during ultrasound examination. In the second case, the metastasis was observed during regular follow-up.. The diagnosis was established based on the histological features and immunohistochemical profile that showed positivity for vimentin, nuclear β-catenin, cyclin D1, CD10, and SRY-related high-mobility group box 11 and negativity for maspin.. Surgical excision, in both cases.. No recurrences in first case, at 5 months after diagnosis. Hepatic metastases in the second case, at 13 years after diagnosis, with portal invasion after another 15 months.. Without a complex immunoprofile, SPN can be misdiagnosed as NET. SPN can be a low-grade tumor but long-time follow-up is mandatory to detect delayed metastases. A correct diagnosis is necessary for a proper therapeutic management.

Topics: Adenocarcinoma, Papillary; Adult; beta Catenin; Biomarkers, Tumor; Cyclin D1; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Middle Aged; Neoplasms, Cystic, Mucinous, and Serous; Neprilysin; Neuroendocrine Tumors; Pancreas; Pancreatectomy; Pancreatic Neoplasms; Prognosis; Treatment Outcome; Vimentin

BACKGROUND Many findings have shown that pyruvate kinase type M2 (PKM2) plays crucial roles in regulating the occurrence and development of various human cancers; however, its roles in ovarian cancer oncogenesis remain to be determined. MATERIAL AND METHODS The expression intensity of PKM2 in ovarian cancer tissues was examined by immunohistochemistry (IHC), and was then correlated to patient clinicopathologic characteristics. The roles of PKM2 in ovarian cancer cell proliferation, growth, and survival were examined by CCK-8, colony forming, and flow cytometry assays. The potentially involved molecular were then investigated by Western blot analysis. RESULTS IHC results showed that PKM2 was overexpressed in 100 of 114 (87.7%) serous ovarian cancer tissues as compared with 50 cases of non-cancerous ovarian tissues, and was associated with tumor size ≥7.5 cm and <7.5 cm (p<0.05). Overexpression of PKM2 in SKOV3 and HEY ovarian cancer cells by transfection with PKM2 lentivirus vector led to increased cell proliferation, growth, and survival, which may be related with PKM2 being able to increase cell cycle progress: G1 stage decreased, whereas S stage significantly increased. In contrast, all functions of SKOV3 and HEY cells described above were reversed by knocked down PKM2 expression using siRNA. Further data showed that overexpressed PKM2 led to increased CCND1 and decreased CDKN1A expression, whereas underexpressed PKM2 led to decreased CCND1 and increased CDKN1A expression in ovarian cancer cells. CONCLUSIONS PKM2 may play important roles in ovarian cancer development and may be a treatment target for this cancer.

Topics: Apoptosis; Carrier Proteins; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p21; Down-Regulation; Female; Flow Cytometry; Gene Expression Regulation, Neoplastic; Humans; Membrane Proteins; Neoplasms, Cystic, Mucinous, and Serous; Ovarian Neoplasms; S Phase; Survival Analysis; Thyroid Hormone-Binding Proteins; Thyroid Hormones; Tumor Stem Cell Assay; Up-Regulation

The most prevalent malignant ovarian neoplasms are epithelial ovarian cancers which is the most common cause of death among all gynecologic malignancies and a result of complex interaction of multiple oncogenes and tumor suppressor genes. The aim of this study was to evaluate expression of survivin and cycline D1 biomarkers in mucinous ovarian neoplasms and their correlations with clinicopathological variables in mucinous ovarian cancers. We analyzed pathological specimens of 98 patients with benign (n = 34), borderline (n = 22) and malignant (n = 42) mucinous ovarian neoplasms. Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded specimens. Immunohistochemical analysis revealed that survivin and cyclin D1 expressions were located primarily in the nucleus of ovarian tumor cells and relatively weaker cytoplasmic staining. Survivin expression was significantly higher in malignant tumors (88.1 %) than those found in borderline (18.2 %) and benign tumors (8.8 %) (p < 0.001). Similarly, higher cyclin D1 expression was observed in malignant tumors (100 %) compared to borderline (36.4 %) and benign tumors (5.9 %) (p < 0.001). Expression of all biomarkers analyzed significantly and gradually increased from benign to borderline and borderline to malignant mucinous tumors. In terms of clinicopathological variables, tumor grade, FIGO stage and lymph node methastasis were associated with the expression of both biomarkers. Whereas age exhibited no different correlations in mucinous ovarian cancers. The expressions of survivin and cycline D1 are positively correlated with the malignant potential of mucinous ovarian neoplasms.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cell Nucleus; Cyclin D1; Female; Humans; Inhibitor of Apoptosis Proteins; Middle Aged; Neoplasms, Cystic, Mucinous, and Serous; Ovarian Neoplasms; Survivin; Young Adult

Since our first description of the microcystic stromal tumor (MST) of the ovary, a rare and distinctive neoplasm with a definitional, usually striking microcystic pattern and a CD10+/vimentin+/inhibin-/calretinin- immunophenotype, 3 examples with β-catenin nuclear localization, and CTNNB1 mutation have been reported. We undertook a detailed immunohistochemical study and molecular analysis of CTNNB1 and FOXL2 of 15 cases of MST to further characterize this neoplasm and establish its histogenesis. Diffuse nuclear staining for FOXL2, WT-1, cyclin D1, and β-catenin was present in all tumors tested, and 12/15 were positive for steroidogenic factor-1 (SF-1). Heterozygous missense point mutations in exon 3 of CTNNB1 were detected in 8 of 14 cases, resulting in amino acid changes at codons 32, 34, 35, and 37. There was no correlation between CTNNB1 exon 3 mutation status and tumor immunophenotype. All 14 cases tested showed wild-type FOXL2. Our study establishes that MST of the ovary exhibits a characteristic FOXL2/SF-1/WT-1/cyclin D1/nuclear β-catenin-positive immunohistochemical profile, which may be useful in diagnosis and in the exclusion of histologic mimics. The presence of diffuse nuclear FOXL2 and WT-1 immunostaining in all cases and SF-1 in most supports the classification of MST within the sex cord-stromal category. Aberrant nuclear β-catenin expression, detected in all MSTs, appears to be the result of stabilizing CTNNB1 mutations in 57% of cases, providing further evidence that dysregulation of the Wnt/B-catenin pathway is involved in the tumorigenesis of MST and may involve activation of β-catenin with upregulation of cyclin D1.

Topics: Adult; beta Catenin; Biomarkers, Tumor; Cyclin D1; DNA Mutational Analysis; DNA-Binding Proteins; Female; Forkhead Box Protein L2; Forkhead Transcription Factors; Humans; Immunohistochemistry; Middle Aged; Neoplasms, Cystic, Mucinous, and Serous; Ovarian Neoplasms; RNA Splicing Factors; Sex Cord-Gonadal Stromal Tumors; Transcription Factors; Wnt Signaling Pathway; WT1 Proteins

Ovarian cancer is the most common cause of death among all gynecologic malignancies and a result of complex interaction of multiple oncogenes and tumor suppressor genes. The aim of this study was to evaluate expression of HER-2/neu (c-erbB2), survivin and cycline D1 biomarkers in serous ovarian neoplasms and their correlations with clinicopathological variables in serous ovarian cancers. We analyzed pathological specimens of 62 patients with benign (n = 25), borderline (n = 14) and malignant (n = 23) serous ovarian neoplasms. Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded specimens. Significantly more immunoreactivity with HER-2/neu was detected in malignant tumors (100 %) compared to borderline (78.6 %) and benign tumors (48 %) (P < 0.01). Survivin expression was significantly higher in malignant tumors (91.3 %) than those found in borderline (71.4 %) and benign tumors (24 %) (P < 0.001). Similarly, higher cyclin D1 expression was observed in malignant tumors (95.6 %) compared to borderline (85.7 %) and benign tumors (48 %) (P < 0.001). Expression of all biomarkers analyzed significantly and gradually increased from benign to borderline and borderline to malignant serous tumors. In terms of clinicopathological variables, only tumor grade was associated with the expression of all biomarkers others exhibited different correlations in serous ovarian cancers. The expressions of HER-2/neu (c-erbB2), survivin and cycline D1 are positively correlated with the malignant potential of serous ovarian neoplasms.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cyclin D1; Female; Humans; Inhibitor of Apoptosis Proteins; Middle Aged; Neoplasms, Cystic, Mucinous, and Serous; Ovarian Neoplasms; Receptor, ErbB-2; Survivin; Young Adult

Alteration of CyclinD1 was suggested to relate with development of endometrial carcinogenesis before, however CyclinD1 expression is not well defined in endometrial hyperplasia lesions. We checked the relationship between its expression and clinic-pathological variables of endometrial lesions to explore the possibility for CyclinD1 as a potential diagnostic and prognostic marker.. Cyclin D1 immunohistochemical analysis (IHC) was used to evaluate 201 fixed, paraffin-embedded endometrial samples which included simple hyperplasia (n = 27), atypical complex hyperplasia (ACH) (n = 41), endometrioid carcinoma (n = 103), endometrial serous carcinoma (ESC) (n = 21) and clear cell carcinoma (CCC) (n = 9). A breast cancer with known CyclinD1 expression was selected as a positive control in each immunohistochemistry run. We also performed follow-up study to estimate patients' prognosis.. CyclinD1 was significantly overexpressed in atypical complex hyperplasia (ACH), endometrioid carcinoma and clear cell carcinoma (CCC). The positive signaling of CyclinD1 was showed less than 40% in simple hyperplasia and endometrial serous carcinoma (ESC). The high expression of CyclinD1 was observed in metastasis carcinoma group more significantly than non-metastasis carcinoma group. Kaplan Meier analysis demonstrated that patients with high CyclinD1 expression had an obviously poor prognosis than patients without CyclinD1 staining (p < 0.05). Moreover, according to multivariate Cox regression analysis, CyclinD1 expression, as crucial as metastasis, was a risk marker for overall survival rate.. CyclinD1 exhibited a promising potential to predict the prognosis of patients with endometrial carcinoma. However, the statistical analysis demonstrated that CyclinD1 exhibited a poor ability to differentiate neoplastic lesions from non-neoplastic lesions; thus, the application of CyclinD1 only is not so credible for differentiation between benign and malignant lesions.. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1871063048950173.

Topics: Adenocarcinoma, Clear Cell; Adult; Biomarkers, Tumor; Biopsy; Carcinoma, Endometrioid; Chi-Square Distribution; Cyclin D1; Endometrial Hyperplasia; Endometrial Neoplasms; Endometrium; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Middle Aged; Multivariate Analysis; Neoplasms, Cystic, Mucinous, and Serous; Prognosis; Proportional Hazards Models; Risk Factors; Time Factors; Up-Regulation