BACKGROUND: Stathmin, a cytosolic microtubule-destabilizing phosphoprotein involved in the regulation of mitosis, is widely expressed in various malignancies and acts as an adverse prognostic factor. Our research analyzed its immunohistochemical expression on a large cohort of ovarian sex cord-stromal tumors, evaluating its potential utility in differential diagnosis, prognosis, and therapeutic application. METHODS: We examined 390 cases of ovarian sex cord-stromal tumors including 281 adult granulosa cell tumors (AGCT), 5 juvenile granulosa cell tumors (JGCT), 33 Sertoli-Leydig cell tumors (SLCT), 50 fibromas/thecomas (F/T), 11 Leydig cell tumors/steroid cell tumors (LCT/SterCT), 5 sex-cord stromal tumors NOS (SCST-NOS), 3 Sertoli cell tumors (SCT), and 2 sclerosing stromal tumors (ScST). Immunohistochemical analysis was performed using TMAs. RESULTS: Strong expression (> 50%) was observed in all cases of AGCT, JGCT, SLCT, SCST-NOS, SCT and 1 ScST. The other case of ScST exhibited mild expression (5-10%). The negative cases included exclusively F/T and LCT/SterCT, with F/T showing 24% of negative cases and LCT/SterCT comprising 64% of negative cases. CONCLUSION: The results of our study indicate that stathmin is neither a prognostic marker nor suitable for the differential diagnosis of challenging cases of ovarian sex cord-stromal tumors. However, its predictive value may be theoretically significant, as a decrease in stathmin expression potentialy influences response to chemotherapy treatment.
- MeSH
- Diagnosis, Differential MeSH
- Adult MeSH
- Sex Cord-Gonadal Stromal Tumors * pathology diagnosis metabolism therapy MeSH
- Immunohistochemistry * MeSH
- Middle Aged MeSH
- Humans MeSH
- Biomarkers, Tumor * analysis MeSH
- Ovarian Neoplasms * pathology diagnosis metabolism therapy MeSH
- Prognosis MeSH
- Stathmin * analysis metabolism MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
A specific form of endometrial cancer (EC) can develop in breast cancer patients previously treated with tamoxifen (ET), an antagonist of estrogen receptor (ER) that inhibits proliferation of ER positive breast cancer. ET tumors have a different phenotype than endometrial tumors, which typically develop de novo without previous exposure to tamoxifen (EN). Here we aimed to identify specific protein markers that could serve as specific molecular targets in either phenotype. A set of total 45 formalin-fixed paraffin-embedded (FFPE) endometrial tumor tissues and adjacent myometrium tissue samples were analyzed using LC-MS/MS in SWATH-MS mode. We found that calcyphosin (CAPS) levels were elevated in EN tumors compared to ET tumors. The higher CAPS level in EC tissue invading to myometrium supports its relationship to EC aggressiveness. Further, stathmin (STMN1) levels were found significantly elevated in ET versus EN tumors and significantly associated with patient survival. This finding connects elevated levels of this cell cycle regulating, proliferation-associated protein with tamoxifen exposure. In summary, using SWATH-MS we show that CAPS and STMN1 should be recognized as clinicopathologically different EC markers of which STMN1 is specifically connected with a previous tamoxifen exposition.
- MeSH
- Chromatography, Liquid MeSH
- Humans MeSH
- Endometrial Neoplasms * drug therapy MeSH
- Breast Neoplasms * MeSH
- Stathmin genetics MeSH
- Tamoxifen adverse effects MeSH
- Tandem Mass Spectrometry MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
In several solid tumors, an increased stathmin expression is associated with both poor prognosis and resistance to certain chemotherapy types. However, the data regarding melanocytic lesions are very limited. The goals of our study are as follows: the assessment of stathmin expression in benign and malignant melanocytic lesions, and the significance of its expression for the differential diagnostics between benign and malignant lesions; the analysis of the prognostic significance of stathmin expression in melanoma; and the evaluation of stathmin expression in melanoma and melanoma metastases with respect to possible therapeutic targeting. Immunohistochemical analysis of stathmin expression was done in 323 melanocytic lesions, including 205 primary cutaneous melanomas, 60 melanoma metastases, and 58 melanocytic nevi. Stathmin expression was found in all analyzed groups of melanocytic lesions. Using the H-scoring system, the observed intensity of expression was as follows: melanocytic nevi: 146.1 (mean) and 150 (median); melanomas: 116.7 (mean) and 110 (median); and melanoma metastases: 136.8 (mean) and 140 (median). The stathmin expression was significantly lower in the cohort of primary melanomas when compared with metastases and nevi (P=0.001). The stathmin expression showed no prognostic significance. The high stathmin expression in melanoma suggests that stathmin might be a promising marker for therapeutic targeting in ongoing clinical trials. Compared with several other solid tumors, stathmin expression in melanoma showed no prognostic significance. The potential use of stathmin expression in differential diagnostics is limited by its common expression, and despite the statistically significant differences between nevi and melanoma, it may not be used in this setting.
- MeSH
- Immunohistochemistry MeSH
- Middle Aged MeSH
- Humans MeSH
- Melanocytes metabolism pathology MeSH
- Melanoma blood pathology MeSH
- Biomarkers, Tumor metabolism MeSH
- Skin Neoplasms blood pathology MeSH
- Prognosis MeSH
- Stathmin metabolism MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Breast cancer is the most common and molecularly relatively well characterized malignant disease in women, however, its progression to metastatic cancer remains lethal for 78% of patients 5years after diagnosis. Novel markers could identify the high risk patients and their verification using quantitative methods is essential to overcome genetic, inter-tumor and intra-tumor variability and translate novel findings into cancer diagnosis and treatment. We recently identified 13 proteins associated with estrogen receptor, tumor grade and lymph node status, the key factors of breast cancer aggressiveness, using untargeted proteomics. Here we verified these findings in the same set of 96 tumors using targeted proteomics based on selected reaction monitoring with mTRAQ labeling (mTRAQ-SRM), transcriptomics and immunohistochemistry and validated in 5 independent sets of 715 patients using transcriptomics. We confirmed: (i) positive association of anterior gradient protein 2 homolog (AGR2) and periostin (POSTN) and negative association of annexin A1 (ANXA1) with estrogen receptor status; (ii) positive association of stathmin (STMN1), cofilin-1 (COF1), plasminogen activator inhibitor 1 RNA-binding protein (PAIRBP1) and negative associations of thrombospondin-2 (TSP2) and POSTN levels with tumor grade; and (iii) positive association of POSTN, alpha-actinin-4 (ACTN4) and STMN1 with lymph node status. This study highlights a panel of gene products that can contribute to breast cancer aggressiveness and metastasis, the understanding of which is important for development of more precise breast cancer treatment.
- MeSH
- Adult MeSH
- Actin Depolymerizing Factors biosynthesis genetics MeSH
- Neoplasm Invasiveness genetics pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Lymphatic Metastasis MeSH
- Lymph Nodes metabolism pathology MeSH
- Cell Adhesion Molecules biosynthesis genetics MeSH
- Biomarkers, Tumor biosynthesis genetics MeSH
- Neoplasm Proteins biosynthesis genetics MeSH
- Breast Neoplasms genetics pathology MeSH
- Disease-Free Survival MeSH
- Prognosis MeSH
- RNA-Binding Proteins biosynthesis genetics MeSH
- Proteomics MeSH
- Receptors, Estrogen genetics MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Aged MeSH
- Stathmin biosynthesis genetics MeSH
- Thrombospondins biosynthesis genetics MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
