ABSTRACT
SUMMARY: Uterine smooth muscle tumors (USMT) are common, behavior-distinct gynecological tumors; including: leiomyoma (ULM), leiomyosarcoma (ULMS), and smooth muscle tumors of undetermined malignant potential (STUMP). Pre-operative distinction is difficult, thus diagnosis relies on histopathology. Immunohistochemistry (IHC) had been used to help in distinction. We studied two markers (stathmin-1 and CD147) to demonstrate whether they have diagnostic/ prognostic assist. Sixty seven USMT are studied. Age, follow up, and recurrence/metastasis data were collected. Representative slides were stained and Histologic score (HS) calculated as stain intensity (SI) X percentage of positive tumor cells (PP). Results were grouped as low expression (LE) and high expression (HE); then correlated to tumor types, and risk of recurrence/ metastasis. Statistical analysis (P < 0.05); Sensitivity, specificity, positive and negative predictive values and confidence intervals in diagnosing ULMS were calculated. Stathmin-1 HS (p= 0.000) and HE (p=0.002) were different among groups. Same as for CD147 HS and HE (both p=0.000), with a gradient increase from LM to STUMP to ULMS. Sensitivity, specificity, positive and negative predictive values and confidence intervals in diagnosing ULMS were as following: For stathmin-1 HS: 92 %; 20 %; 42 %; and 80 % (CI= 44-96 %). For Stathmin-1 HE: 80 %; 66 %; 60 %; and 84 % (CI=66-94 %). For CD147 HS: 85 %; 22 %; 41 %; and 69 %. For CD147 HE: 58 %; 49 %; 42 %; and 65 % (CI= 45-80 %), respectively. Recurrence / metastasis were documented in 6 cases (4 ULMS; 2 STUMP) with follow up ranging from 6 months to 102 months. 5 tumors had stathmin-1 HE (p=0.099); 2 had CD147 HE (p=0.393) in the primary tumors. STMN1 and CD147 are helpful diagnostic tests for USMT sub-typing, especially for ULMS. Gradient increase of expression from LM, to STUMP, to ULMS may indicate a role in malignant transformation in USMT, and in increased risk of recurrences/metastasis.
RESUMEN: Los tumores del músculo liso uterino (USMT, por sus siglas en inglés) son tumores ginecológicos comunes y de comportamiento distinto; incluyendo: leiomioma (ULM), leiomiosarcoma (ULMS) y tumores de músculo liso de potencial maligno indeterminado (STUMP). La distinción preoperatoria es difícil, por lo que el diagnóstico se basa en la histopatología. La inmunohistoquímica (IHQ) se había utilizado para ayudar en la distinción. Estudiamos dos marcadores (stathmin-1 y CD147) para demostrar si había efecto diagnóstico / pronóstico. Se estudiaron 67 USMT. Se recopilaron los datos de edad, seguimiento y recurrencia / metástasis. Las muestras representativas se tiñeron y la puntuación histológica (HS) se calculó como la intensidad de la tinción (IS) x porcentaje de células tumorales positivas (PP). Los resultados se agruparon como expresión baja (EB) y expresión alta (EA); luego se correlacionaeon con los tipos de tumores y el riesgo de recurrencia / metástasis. Análisis estadístico (P <0,05); se calcularon la sensibilidad, la especificidad, los valores predictivos positivos y negativos y los intervalos de confianza en el diagnóstico de ULMS. Stathmin-1 HS (p = 0,000) y HE (p = 0,002) fueron diferentes entre los grupos. Igual que para CD147 HS y HE (ambos p = 0,000), con un aumento de gradiente de LM a STUMP a ULMS. La sensibilidad, la especificidad, los valores predictivos positivos y negativos y los intervalos de confianza en el diagnóstico de ULMS fueron los siguientes: Para stathmin-1 HS: 92 %; 20 %; 42 %; y 80 % (IC = 44-96 %). Para Stathmin-1 HE: 80 %; 66 %; 60 %; y 84 % (IC = 66-94 %). Para CD147 HS: 85 %; 22 %; 41 %; y el 69 %. Para CD147 HE: 58 %; 49 %; 42 %; y 65 % (IC = 45-80 %), respectivamente. La recurrencia / metástasis se documentaron en 6 casos (4 ULMS; 2 STUMP) con un seguimiento que osciló entre 6 meses y 102 meses. Cinco tumores tenían stathmin-1 HE (p = 0,099); dos tenían CD147 HE (p = 0,393) en los tumores primarios. STMN1 y CD147 son pruebas de diagnóstico útiles para la subclasificación de USMT, especialmente para ULMS. El aumento en el gradiente de la expresión de LM, a STUMP, a ULMS puede indicar un papel en la transformación maligna en USMT y en un mayor riesgo de recurrencias / metástasis.
Subject(s)
Humans , Female , Adult , Middle Aged , Uterine Neoplasms/diagnosis , Smooth Muscle Tumor/diagnosis , Stathmin/metabolism , Basigin/metabolism , Uterine Neoplasms/metabolism , Uterine Neoplasms/pathology , Immunohistochemistry , Confidence Intervals , Predictive Value of Tests , Sensitivity and Specificity , Smooth Muscle Tumor/metabolism , Smooth Muscle Tumor/pathology , Leiomyoma/diagnosis , Leiomyoma/pathology , Leiomyosarcoma/diagnosis , Leiomyosarcoma/pathologyABSTRACT
AIM:To investigate the clinical significance of stathmin 1 (STMN1) expression in cervical cancer and the influence of its expression on the viability and apoptosis of cervical cancer cells. METHODS:Western blot was used to detect the protein expression of STMN1 in cervical cancer tissues, and the relationship between the expression and clinical characteristics of cervical cancer was analyzed. STMN1-siRNA was transfected into cervical squamous-cell carcino-ma SiHa cells. The protein levels of STMN1, STAT3, p-STAT3 and survivin were determined by Western blot after trans-fection for 48 h. The cell viability was measured by MTT assay. The apoptosis was analyzed by flow cytometry. DCFH-DA probe was used to detect the level of reactive oxygen species (ROS). RESULTS:The protein expression of STMN1 in cer-vical cancer tissues was significantly higher than that in paracancerous tissues (P<0.01). The STMN1 protein expression level was not correlated with age and histological types of cervical cancer patients, but was related to clinical stage, histo-logical differentiation and lymph node metastasis ( P<0.01). Transfection with STMN1-siRNA significantly reduced the expression of STMN1 in SiHa cells. Compared with control group, the cell viability in STMN1-siRNA group was significant-ly decreased, the apoptotic rate and ROS content were increased, and the protein levels of p-STAT3 and survivin were down-regulated (P<0.01). However, no significant difference of the STAT3 protein level was observed between STMN1- siRNA group and control group. CONCLUSION:STMN1 is highly expressed in cervical cancer, and its expression is re-lated to clinical stage, histological differentiation and lymph node metastasis. Inhibition of STMN1 expression reduces the viability and promotes apoptosis of cancer cells by down-regulating STAT3 signaling pathway.
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Objective To explore the relationship between Stathmin-1 and human papilloma viruse (HPV) persistent infection after conization of uterine cervix, and to show the clinical significance to recurrent of cervical intraepithelial neoplasia (CIN). Methods One hundred and six patients who were treated with conization of uterine cervix for CIN 2-3 grades were enrolled. Thirty-six recurrent patients were enrolled in recurrence group, and the others were enrolled in control group. The expression of Stathmin-1 in primary CIN tissues in two groups was detected by immunohistochemistry. The HPV infection was detected by HPV-DNA test. The relationship of HPV persistent infection and recurrence was analyzed. Results The positive expression rate of HPV persistent infection and HPV persistent infection rate in recurrence group were 88.89%(32/36), 83.33%(30/36), in control group were 34.29%(24/70) and 22.86%(16/70), and there were significant difference (P 0.05). Conclusions Stathmin-1 positive expression is related to HPV persistent infection. The two factors can affect the prognosis of high-grade CIN, and can provide new cues and theory basis for the prevention of recurrence.
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Objective To screen the differential expression proteins in the children with neuroblastoma (NB) by proteomics tools.Methods Three specimens were collected from the patients diagnosed Ⅳstage NB by biopsy at Department of Pediatric Surgery of Chinese PLA General Hospital in Beijing from July to December,2011.Another three specimens were acquired from the same patients underwent tumor excision.Average age was 3.17 years.Proteins in neuroblastoma before and after chemotherapy were separated by two dimensional gel electrophoresis,analyzed by high performance liquid chromatography-eleetrospray tandem MS (Nano-UPLC-ESIMS/MS).Results After two dimensional gel electrophoresis,we obtained the maps about tissues before and after chemotherapy.There were 7 differential protein spots identified by using the Image Master two dimensional gel electrophoresis software,in which 2 were up-regulated,including Nm23 protein and neuropolypeptide h3,5were down-regulated after chemotherapy,including stathminl,heat shock protein 27,mitochondrial short-chain enoyl-coenzyme A,peroxiredoxin 1 and peroxiredoxin 3.Conclusion The differential expression proteins of children neuroblastoma before and after chemotherapy were successfully identified by two dimensional gel electrophoresis and Nano-UPLC-ESI-MS/MS.
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Objective To investigate the effects of monoclonal antibody against stathmin 1 in combination with vinblastine on the proliferation of K562 cells. Methods K562 cells were treated with monoclonal antibody against stathmin 1, vinblastine alone or with their combination, 24, 48, 72, 96 hours later, inhabitation rate was studied by MTT assay;The apoptosis was analyzed by invert microscope and flow cytometry with Annexin V/PI. Results The quantity decreased and shape, size changed after treatment with different concentration of experimental groups. Monoclonal antibodies against stathmin 1 and vinblastine used alone or in combination both inhibited the proliferation of K562 cells,the inhibition ratio of their combination is higher (P <0. 05) ,and a synergistic effect of the two agents was noted in their combined action ( P < 0. 05 ). Combined treatment of the cells resulted in significantly higher apoptsis rate than that in the other groups (P <0. 05). Conclusion Monoclonal antibody against stathmin 1 and vinblastine used alone or in combination both can inhibite proliferation of K562 cells and induce apoptsis. A synergistic effect is observed between the monoclonal antibodies against stathmin 1 and vinblastine in their inhibition of K562 cell proliferation.