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Objective To evaluate the role of mitochondrial calcium uniporter ( MCU) in mitoph-agy in SH-SY5Y cells subjected to oxygen-glucose deprivation and restoration (OGD∕R). Methods SH-SY5Y cells were cultured in vitro, seeded in 96-well plates at a density of 2×105cells∕ml, and randomly di-vided into 4 groups (n=6 each) using a random number table method: control group (group C), group OGD∕R, OGD∕R plus MCU inhibitor group ( group OGD∕R + Ru360) and MCU inhibitor group ( group Ru360) . Cells were cultured in normal culture medium in group C. Cells were subjected to O2-glucose dep-rivation for 6 h followed by restoration of O2-glucose supply for 24 h in group OGD∕R. In group OGD∕R+Ru360, Ru360 at a final concentration of 10 μmol∕L was added at 30 min before O2-glucose deprivation, and the other treatments were similar to those previously described in group OGD∕R. Ru360 was added at a final concentration of 10 μmol∕L, and 30 min later cells were cultured under normoxic conditions in group Ru360. At 24 h of restoration of O2-glucose supply, cell counting kit-8 assay was used to detect the cell survival rate, JC-1 assay was used to detect mitochondrial membrane potential ( MMP ) , the ultrastructure of cells was observed with a transmission electron microscope, and the expression of p62, Tom20 and Bec-lin-1 was detected by Western blot. Results Compared with group C, no significant change was found in each parameter in group Ru360 ( P>0. 05) , the cell survival rate and MMP were significantly decreased, the expression of Tom20 and p62 was down-regulated, Beclin-1 expression was up-regulated (P<0. 01), the mitochondria swelled, and mitochondrial autophagosomes were increased in group OGD∕R. Compared with group OGD∕R, the cell survival rate and MMP were significantly increased, the expression of Tom20 and p62 was up-regulated, Beclin-1 expression was down-regulated (P<0. 01), the mitochondrial mor-phology kept well, and mitochondrial autophagosomes were decreased. Conclusion MCU is involved in the process of mitophagy in SH-SY5Y cells subjected to OGD∕R.
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Objective@#To study the clinicopathologic features, immunophenotype, characteristic FISH pattern and prognosis of renal cell carcinoma (RCC) associated with chromosome X inversion harboring gene fusions involving TFE3.@*Methods@#Ten cases of NONO-TFE3 RCC and four cases of RBM10-TFE3 RCC were investigated at Nanjing Jinling Hospital from 2009 to 2016 by clinicopathological findings, immunohistochemistry, and genetic analysis.@*Results@#Morphologically, the distinct pattern of secretory endometrioid subnuclear vacuolization was overlapped with clear cell papillary RCC, and often accompanied by sheets of epithelial cells in NONO-TFE3 RCC. Most cases of RBM10-TFE3 RCC presented with the biphasic feature that acinar, tubular and papillary patterns of epithelioid cells combined with sheets of small cells with "pseudorosette-like" architectures. In addition, cytoplasmic vacuolization, nuclear groove, and psammoma bodies were also observed. Immunohistochemically, all NONO-TFE3 RCC cases were immunoreactive for TFE3, CD10, RCC markers, and PAX8, and negative for CK7, Cathepsin K, Melan A, HMB45, Ksp-cadherin, vimentin, and CD117. All 4 cases of RBM10-TFE3 RCC showed moderate to strong immunoreactivity for TFE3, Cathepsin K, CD10, Ksp-cadherin, E-cadherin, P504s, RCC marker, PAX8, and vimentin but negative for TFEB, HMB45 and CK7. CKpan and Melan A were at least focally expressed. The antibody to Ki-67 showed labeling of 3%-8% (mean 5%). There were some expression discrepancies of immunochemistry between different histological patterns. PAX8, CKpan, P504s, and Ksp-cadherin were expressed in epithelioid areas but not in small-cell areas. Ki-67 labeling index of epithelioid areas was higher than that in small-cell areas. In molecular analysis, NONO-TFE3 fusion transcripts were identified in 6 patients. The fusion points were between exon 7 of NONO and exon 6 of TFE3 in 5 patients and between exon 9 of NONO and exon 5 of TFE3 in one patient. All 4 cases of RBM10-TFE3 RCC demonstrated to have RBM10-TFE3 fusion transcripts and the fusion points were between exon 5 of TFE3 and exon 17 of RBM10. Using TFE3 break-apart FISH assay, all 10 cases of NONO-TFE3 RCC showed characteristic patterns of equivocal split signals with a distance of nearly 2 signal diameters. All 4 cases of RBM10-TFE3 RCC showed colocalized or subtle split signals with a distance of <1 signal diameter, which was considered as negative results. Long-term follow-up was available for 7 patients of NONO-TFE3 RCC and 4 patients of RBM10-TFE3 RCC. All patients were alive with no evidence of disease.@*Conclusions@#Two rare genotypes, NONO-TFE3 RCC and RBM10-TFE3 RCC, are reported in this study. Both of these two tumors show specific morphology and good prognosis, along with the positive TFE3 staining and the equivocal or false-negative TFE3 FISH results, which could be missed. PCR detection or next-generation sequencing can determine the genotype.
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A male patient, 67 years old, was admitted with the left auricle neoplasm over two months, increased rapidly for 10 days, on November 5, 2013. The tumer is about 2. 0 cm ×× 2. 0 cm size, smooth surface, no burst, hard, painless, and immobilization. After admission biopsy, the pathological report: "spindle cell sarcoma", thin a total resection of the left auricle under local anesthesia was made, postoperative pathological report: tumor by short of spindle cells, arranged in bunchiness, a small number of seats is arrangeA striate;The nuclei are hyperchromatic and part of the visible nucleoli and empty bright cytoplasm, pathological nuclear fission was visible. "Scar" on the matrix of collagen, hardening, and change the glass samples. The tumor destruction of cartilage. immunohistochemical stainin : Vimentin (+), CD99 (-), Bcl-2 (-), CD34 (-), SMA (-), Des (-), HMB45 (-), MelanA(-), S-100(-), CK(-). Diagnosis as fibrosarcoma. The patient refused any radiation or chemotherapy. Postoperative follow-up of 8 months, no local recurrence and distant metastasis.
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Aged , Humans , Male , Ear Neoplasms , Diagnosis , Fibrosarcoma , Diagnosis , Neoplasm Recurrence, LocalABSTRACT
Objective To investigate the value of combined detection of serum tumor biomarkers including alpha-fetoprotein (AFP),tumor specific growth factor (TSGF),golgi protein 73 (GP73) and osteopontin (OPN) in diagnosis of primmy hepatic carcinoma.Methods AFP,TSGF and GP73 levels were measured by electro-chemiluminescence immunoassay,and OPN levels by enzyme-linked immunosorbent assay (ELISA) in 122 cases of primary hepatic carcinoma,50 cases of liver benign lesions and 50 cases of healthy control.The biological parameters and the levels of AFP,TSGF,GP73 and OPN were studied.Results The serum levels of AFP,TSGF,GP73 and OPN in primary hepatic carcinoma were higher than those in the liver benign disease group and the normal control group (all P ＜ 0.01).Sex and age of the patients at diagnosis showed no significant association with the levels of the four serum tumor biomarkers in the primary hepatic carcinoma groups (all P ＞ 0.05).But the tumor size,amount,tumor stage,metastasis and recurrence showed significant association with the levels of those in the primary hepatic carcinoma groups (all P ＜ 0.05).The sensitivity,specificity and veracity of serum AFP,TSGF,GP73 and OPN as individual diagnostic marker was only 57.38 ％,68.85 ％,70.49 ％ and 69.67 ％,respectively.The sensitivity of combined detection of AFP and TSGF was 80.33 ％,and that of combined detection of AFP,TSGF and GP73 was 85.25 ％.While,the sensitivity of the four serum tumor markers in combination was 98.36 ％,the accuracy was 95.65 ％.The sensitivity and accuracy of combined detection with the four serum tumor markers were significantly higher than those of the individual markers and other combination detection methods (all P ＜ 0.05).Conclusions Serum markers of AFP,TSGF,GP73 and OPN can serve as a means for diagnosis of primary hepatic carcinoma.Combined detection of the four serum tumor biomarkers can improve the sensitivity,accuracy and the negative predictive value,which is benefit to early diagnosis and interference.
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Objective To study the value of tumor markers of CA153,CEA and CA125 in nipple discharge of breast intraductal papillary leision on detection of breast carcinoma.Methods 154 cases of breast intraductal papillary leision with nipple discharge were studied.Among them there were 58 cases with breast intraductal papillary carcinoma and 96 cases with intraductal papilloma.The nipple discharged and serum from the 154 cases were collected and CA153,CEA and CA125 levels were measured both in nipple discharge and serum with electrochemiluminescence method,and were compared with the results of ER,PR,HIF-1α and Ki-67 detected by SP method in breast tissue.Results The CA153,CEA and CA125 levels of nipple discharge in intraductal papillary carcinoma [(130.1 1±29.62) U/ml,(89.23±28.94) ng/ml,(41.29±16.61) U/ml]were significantly higher than those of the contrast groups,and had a positive correlation with the Ki-67,HIF-1αand lymphnode metastas (P ＜ 0.05),and negative correlation with the level of ER,PR and Her-2 (P ＜ 0.05).The positive rate of CA153,CEA or CA125 in nipple discharge (62.07 ％,46.55 ％,55.17 ％) were significantly higher than that in serum (P ＜ 0.05).The sensitivity of the combined detection of the three tumor markes both in discharge and serum was 96.55 ％,and the negative predictive value was 97.30 ％,which were significantly higher than that in other detection (P ＜ 0.05).Conclusions The positive rate of CA153,CEA and CA125 in nipple discharge were significantly higher than that in serum.The dynamic combined detection of CA153,CEA and CA125 both in nipple discharge and in serum could increase the diagnosis rate of breast intraductal papillary carcinoma.
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Objective To study the relationship between clinical-biological significance and the expression of CD44v6 and Survivin in multifocal papillary thyroid carcinoma (PTC). Methods Immunohistochemical SP method was used to investigate the expression of CD44v6 and Survivin in 47 cases of multifocal PTC and adjacent tissues, and 122 cases of single focal PTC tissues. The expression of CD44v6 and Survivin and the risk factors among different clinical factors were analyzed between solitary PTC and multifocal PTC group. Results Tumor foci were found in 27.8 % (47/169) patients. The patients with multifocal were characterized by a higher ratio of family history of thymid tumor, lymph node metastasis and extra-thymidal extension (χ2 = 4.189, 6.159, 4.079, P ＜0.05), and not related with sex, age, size and the number of the tumors (P ＞0.05).The positive rates of CD44v6 and Survivin were 70.2 % (33/47) and 66.0 %(31/47), respectively, in multifocal PTC, both of which were significantly higher than that in nodular goiter,Hashimoto' s thyroiditis and normal thyroid tissues (χ2 =47.184, P ＜0.05). Overexpressions of CD44v6 and Survivin in multifocal PTC were related to the degree of the infiltration(χ2 = 4.723, P =0.030; χ2 =4.023,P =0.045) and lymph node metastasis (χ2 =5.771, P =0.016; χ2 =5.686, P =0.017), and not related with sex,age, family history and the number of the tumors (P ＞0.05).The expression of CD44v6 was correlated positively with Survivin (r =0.514, χ2 =10.15, P ＜0.01).There was no significant difference in expressions of CD44v6 and Survivin between multifocal and single focal PTC (P ＞0.05).By the sept.2010, the patients with single and mutiple focal PTC were all survival.Conclusion Multifocus is one of the clinical features of PTC.The high expressions of CD44v6 and Survivin in multifocal PTCs relate to the development, invasion and metastasis.
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Objective To study the expression and significance of Ki-67 in gastrointestinal stromal tumors(GIST) with CD117 immunoreactive. Methods The expression of Ki-67 was detected by SP method in 25 cases of high risk GISTS, 18 cases of moderate GISTS and 33 cases of extremely low and low risk GISTS,which were compared with the follow-up results. The relationship between Ki-67 index (LI) and risk degree was analyzed. Results Forty patients with moderate and high risk GIST were followed-up, including 26 alive,12 die of GIST and 2 die of other causes. Compared with patients of extremely low and low risk GIST, Ki-67 LI＞5 % was correlated with moderate and high risk cases (P ＜0.01), meanwhile Ki-67 LI was positively correlated with tumor sizes of ＞5 cm and tumor mitotic cell count ＞5/50 HPF, but was not with locations(P ＞0.05). Conclusion Ki-67 LI＞5 %, tumor size＞5 cm and tumor mitotic cell count＞5/50 HPF are risk indicator for GIST with CD117 immunoreactive.
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Objective To explore the clinical value of combined detection of CA15-3, TSGF, OPN and CA125 in the diagnosis and treatment of breast cancer. Methods The serum specimens from 187 patients with breast cancer (cancer group) were collected, tumor markers CA15-3 and CA125 were detected with electrochemiluminescence method, TSGF was detected with chemocolorimetry, and OPN was detected with enzyme-linked immunosorbent assay. Compared with 50 cases of patients with benign breast disease (control group), The relationship between these marker and clinical stage, recurrence and metastasis of breast cancer were analyzed. Results The serum levels of CA15-3, CA125, TSGF and OPN in cancer group were significantly higher than those in control group (P ＜0.05). Four markers in high clinical stage(Ⅲ and Ⅳ stage)[(83.21±28.67), (89.13±32.34), (278.66±137.23) U/ml and (97.4±11.7) ng/ml, respectively] were higher than those in low stage( Ⅰ and Ⅱ stage) [(60.03±19.35), (58.21±17.56), (155.79±113.11) U/ml and (77.5±10.81) ng/ml,respectively] (P ＜0.05), and those in lymphnode metastasis patients and in recurrence patients were significantly higher than those in corresponding groups (P ＜0.05). The sensitivity and specificity of the combined detection of four tumor markers were 96.3 % (180/187) and 80.0 % (40/50), respectively. The average time of combined detection of serum tumor markers was 2 months ahead of the mammographic features in the recurrence patients with breast cancer. Conclusion The dynamic combined detection of CA15-3, TSGF, OPN and CA125 are better markers for monitoring recurrence and metastasis of breast cancer,which are benefit to early diagnosis and interference.
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Objective To investigate the clinicopathological characteristics and immunopheotype of diffuse large B-cell lymphoma (DLBCL) in order to improve diagnosis and therapy efficacy. Methods The clinical, immunophenotypical and histopathological features of 22 cases of DLBCL patients were studied retrospectively. The expressions of CD20, CD30, CD10, bcl-6, MUM-1, Ki-67 and CD3o of all patients, and CD5,CyclinD1, Lysozyme,AE1/3 and PLAP of patients with differential cancer, seminoma, anaplastic large cell lymphoma and blastic variant of mantle cell lymphoma were detected by EnVision Immunohistochemical technique. Results All patients were primary systemic DLBCL. All of 22 patients, 14 males and 8 females,average 48(21-71) years old, were primary DLBCL, including 13 cases of germinal centre B-cell-like(GCB) (7 cases of intra-node and 6 extra-node) and 9 cases non-GCB (6 intra-node and 3 extra-node). Conclusion The favorable diagnosis of DLBCL may be achieved by combination of clinical histological and immunological features.
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Objective To investigate the clinicopathology characteristics, immunopheotypic of anaplastic large cell lymphoma (ALCL) in order to improve its diagnostic and therapeutic accuracy. Methods The clinical, immunophenotypic and histopathologie features of 19 cases ALCL were retrospectively studied. The expression of CD30, ALK, CD43, CD45RO, EMA and TIA-1 was detected using EnVision immunohistochemical technique. Results All patients were primary systemic ALCL. Among the 19 patients, 11 were males and 8were females. The age ranged from 2 to 71 years, average age 26 years old. It shows a broad morphologic spectrum of the tumor cell and the hallmark cells characterized by sheets of large lymphoid cells withchromatin-poor horseshoe-shaped nuclei containing multiple nucleoli were encountered in all ALCL variants. 16patients (84.2 %) showed B-symptoms, and extranodal involvement was present in 14 (73.7 % ).Immunohistochemical study showed that the tumor cells expressed CD30 (100 %), ALK (78.9 %), EMA(52.6 %), TIA-1 (73.7 %) and 2 cases (10.5 %) neither expressed ALK, nor EMA,TIA-1.17 cases were reached the correct diagnosis according to combination of clinic, histological and immunological features.Conclusion The correct diagnosis of ALCL may be reached by combination of clinic, histological and immunological features according to WHO classification. Immunohistoehemical staining for CD30, ALK, EMA and TIA-1 is useful in making a correct diagnosis.
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Objective To study the clinicopathological characteristics of hepatobiliary cystic neoplasms(cystadenoma and cystadenocarcinoma)in order to improve its diagnostic and therapeutic accuracy.Methods A retrospective analysis was done on the clinical materials of 9 cases of cystic biliary tumors hospitalized in the People's Hospital of Rizhao City from May 1993 to May 2007.All cases were confirmed by operation and pathologic biopsy.Results Six cases were biliary cystadenoma with muhilocular cyst.The other three cases were biliary cystadenocarcinoma,two with single cyst and one with multilocular cyst.Of the three cystadenocarcinorna,two cases had mural nodules and one case had papillary excrescences and cystic wall thickening.Irregular thickening of internal sept.was shown in the multilocular cyst cases.Two had calcification.Enhancement of the wall.internal septa and nlasses were seen in all the malignant tumors on CT scans. Metastatic lymph node was found in one cage. Conclusion There were no special clinical characteristics in difierentiation between hiliary cystadenoma and cystadenocarcinoma. Single cyst, mural nodules and papillary excrescences,irregular thickening of cystic wall and internal septa,coarse calcification and metastatic lymph node increase the likelihood of the diagnosis of the malignant tumors.But the diagnostic differentiation between cystadenoma and cystadenocarcinoma depends on pathology.
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Objective To study the clinicopathology characteristics of chronic lymphocytic thyroiditis (Hashimoto's thymiditis, HT) with occult papillary thyroid carcinoma (occult PTC) in order to improve its diagnostic and therapeutic accuracy. Methods A restrospective analysis was done on the clinical materials of 28 cases of HT with occult PTC from July 1999 to July 2005. All cases were confirmed by operation and pathologic biopsy. Clinical and gross findings were collected. All HE slides were reexamined and immunostains for CK19, galectin-3,and bcl-2 were performed (Envision method). Results In total 189 cases of chronic lymphocytic thyroiditis,28cases (14.8%,28/189)had coexistent occult papillary thyroid carcinoma. There were 19 females and 9 males with median age of 36.7 years old. Normal TSH presented in 11cases (39.3%), high in 8 cases(28.6%), and low in 9cases (32.1%). All tumor diameter was counted for <0.8 cm, 16 cases (57.1%) tumor diameter 0.2～0.5 cm, 12 cases (42.9%) >0.5 cm. Coarse calcification was seen in 6 cases(21.4%) in color ultrasonic exam and CT scans. Follow-up data showed that 28 patients were all alive with no evidence of recurrence or metastasis for 2 to 7 years by December 2007. Conclusion There are no special clinical characteristics in coexistent HT with occult PTC.Coarse calcification in HT in the group of middle-aged women increase the likelihood of the diagnosis. But the diagnosis depends on pathology. Because of the high incidence of occult PTC in HT population, it would be necessary to keep an eye on this particular type of thyroid carcinoma, and multiple sampling in suspected area of HT specimen is advised in the hope not to miss any small tumor in clinical practice.
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Objective To study the expression of Galectin-3,CK19 and Ki-67 in the papillary thyroid carcinoma and papillary thyroid hyperplasia and to find the differential diagnostic makers. Methods A total of 200 cases, including 100 with papillary thyroid carcinoma and 100 papillary thyroid hyperplasia by Immunohistochemistry. Results The positive rates for Galectin-3,CK19 and Ki-67 in the papillary thyroid carcinoma were 100 %, 97 % and 93 %, which were significantly higher than those in the papillary thyroid hyperplasia (13 %, 31 %, 1 %) (P
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Objective To evaluate the barium meal radiography and CT scans in diagnosing malignant gastrointestinal stromal tumors (GIST) of small intestine. Methods The clinical and imaging data of 16 patients with GISTs of small intestine which were diagnosed surgically and pathologically were analyzed and summarized. In this group CT scan and gastrointestinal barium exam(GI) was performed. Results The tumors included 6 low-malignant GISTs of small intestine and 10 high-malignants. The diameter varied from 3.2 cm to 7.2 cm, the average size was 5.6 cm. The main signs of barium meal of malignant GIST of small intestine included flattened or destroyed mucosa runae, partial lumen stenosis, and barium fleck and fistula in the tumor. On CT scans, the main manifestation was an extraluminal mass with multiple necrosis areas of low density. Conclusion Barium examination and helical CT scan are the major imaging techniques in the determination of the location of GIST of small intestine. The appearance of imperfect lumen and the irregular tumor with multiulcerations or low density regions and inhomoneneous enhancement may lead to the correct diagnosis of malignant GIST.