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.
- Klíčová slova
- Immunohistochemistry, Ovarian tumors, Ovary, Sex cord-stromal tumors, Stathmin,
- MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- gonadální stromální nádory * patologie diagnóza metabolismus terapie MeSH
- imunohistochemie * MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery * analýza MeSH
- nádory vaječníků * patologie diagnóza metabolismus terapie MeSH
- prognóza MeSH
- stathmin * analýza metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- nádorové biomarkery * MeSH
- stathmin * MeSH
- STMN1 protein, human MeSH Prohlížeč
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.
- Klíčová slova
- FFPE, SWATH-MS, calcyphosin, endometrial cancer, stathmin,
- MeSH
- chromatografie kapalinová MeSH
- lidé MeSH
- nádory endometria * farmakoterapie MeSH
- nádory prsu * MeSH
- stathmin genetika MeSH
- tamoxifen škodlivé účinky MeSH
- tandemová hmotnostní spektrometrie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- stathmin MeSH
- STMN1 protein, human MeSH Prohlížeč
- tamoxifen MeSH
To assess the potential role of IL-6 in sciatic nerve injury-induced activation of a pro-regenerative state in remote dorsal root ganglia (DRG) neurons, we compared protein levels of SCG-10 and activated STAT3, as well as axon regeneration in IL-6 knockout (IL-6ko) mice and their wild-type (WT) counterparts. Unilateral sciatic nerve compression and transection upregulated SCG-10 protein levels and activated STAT3 in DRG neurons not only in lumbar but also in cervical segments of WT mice. A pro-regenerative state induced by prior sciatic nerve lesion in cervical DRG neurons of WT mice was also shown by testing for axon regeneration in crushed ulnar nerve. DRG neurons from IL-6ko mice also displayed bilaterally increased levels of SCG-10 and STAT3 in both lumbar and cervical segments after sciatic nerve lesions. However, levels of SCG-10 protein in lumbar and cervical DRG of IL-6ko mice were significantly lower than those of their WT counterparts. Sciatic nerve injury induced a lower level of SCG-10 in cervical DRG of IL-6ko than WT mice, and this correlates with significantly shorter regeneration of axons distal to the crushed ulnar nerve. These results suggest that IL-6 contributes, at the very least, to initiation of the neuronal regeneration program in remote DRG neurons after unilateral sciatic nerve injury.
- Klíčová slova
- Primary sensory neuron, SCG10, STAT3, Sciatic nerve lesion, Ulnar nerve crush,
- MeSH
- imunohistochemie MeSH
- interleukin-6 analýza nedostatek metabolismus MeSH
- intracelulární signální peptidy a proteiny analýza MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- neurony chemie cytologie metabolismus patologie MeSH
- poranění periferního nervu metabolismus patologie chirurgie MeSH
- proteiny vázající vápník MeSH
- regenerace nervu * MeSH
- spinální ganglia cytologie metabolismus patologie chirurgie MeSH
- stathmin MeSH
- transkripční faktor STAT3 analýza MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- interleukin-6 MeSH
- intracelulární signální peptidy a proteiny MeSH
- proteiny vázající vápník MeSH
- Stat3 protein, mouse MeSH Prohlížeč
- stathmin MeSH
- Stmn2 protein, mouse MeSH Prohlížeč
- transkripční faktor STAT3 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
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- melanocyty metabolismus patologie MeSH
- melanom krev patologie MeSH
- nádorové biomarkery metabolismus MeSH
- nádory kůže krev patologie MeSH
- prognóza MeSH
- stathmin metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- nádorové biomarkery MeSH
- stathmin 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.
- Klíčová slova
- Breast cancer, Estrogen receptor, Lymph node, Selected reaction monitoring, Tumor grade, mTRAQ,
- MeSH
- dospělí MeSH
- faktory depolymerizující aktin biosyntéza genetika MeSH
- invazivní růst nádoru genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfatické metastázy MeSH
- lymfatické uzliny metabolismus patologie MeSH
- molekuly buněčné adheze biosyntéza genetika MeSH
- nádorové biomarkery biosyntéza genetika MeSH
- nádorové proteiny biosyntéza genetika MeSH
- nádory prsu genetika patologie MeSH
- přežití bez známek nemoci MeSH
- prognóza MeSH
- proteiny vázající RNA biosyntéza genetika MeSH
- proteomika MeSH
- receptory pro estrogeny genetika MeSH
- regulace genové exprese u nádorů MeSH
- senioři MeSH
- stathmin biosyntéza genetika MeSH
- thrombospondiny biosyntéza genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- faktory depolymerizující aktin MeSH
- molekuly buněčné adheze MeSH
- nádorové biomarkery MeSH
- nádorové proteiny MeSH
- POSTN protein, human MeSH Prohlížeč
- proteiny vázající RNA MeSH
- receptory pro estrogeny MeSH
- SERBP1 protein, human MeSH Prohlížeč
- stathmin MeSH
- STMN1 protein, human MeSH Prohlížeč
- thrombospondin 2 MeSH Prohlížeč
- thrombospondiny MeSH
