1.Clinicopathological and molecular pathological features of ovarian micropapillary serous borderline tumor
Fang SONG ; Rulei CHEN ; Xiaoting MA ; Jinghuan LYU
Chinese Journal of Clinical and Experimental Pathology 2024;40(3):255-260
Purpose To investigate the clinicopathological features,immunophenotype,molecular changes,differential di-agnosis,treatment and prognosis of the micropapillary subtype of serous borderline tumor(MSBT)in the ovary.Methods The clinical and pathological data of 14 cases of ovarian MSBT.Im-munohistochemical EnVision staining was used to detect the ex-pression of IMP3.BRAF and KRAS mutations were detected by qRT-PCR and Sanger sequencing,respectively.Its clinical and pathological characteristics were analyzed with review of relevant literature.Results The age of the patients ranged from 27 to 56 years,with mean 41.7 years.Nine cases had bilateral ovari-an masses.Preoperative serum CA125 increased in 11 cases.On gross examination,the cut section was cystic and solid with intracystal papillae.Microscopically,all cases showed a papilla-ry structure,with the characteristic elongated micropapillae radi-ating directly from the cyst wall or large unbranched papillae.The length to width ratio of the papillae was greater than 5.The cells covering the papillae were cubic to polygonal.Mild to mod-erate atypia was noted with a range of>5 mm in the micropapil-lary area.Five cases had microinvasion.Six cases had non-in-vasive peritoneal seeding.Five cases were accompanied by asci-tes,and atypical tumor cells were observed in ascites.Three ca-ses had lymph node involvement.Nine cases had psammoma bodies.Immunohistochemically,the tumor cells were positive for ER,PR,CA125,CK7 and WT-1;p53 was wild type,HER2 and IMP3 were negative,and Ki67 was positive in 5%to 30%.KRAS mutations were detected in 3 of 14 cases,inclu-ding G12C,G12D and Q70(nonsense mutation).No BRAF V600E mutation was detected,and 1 case had BRAF T559I mu-tation.Seven patients underwent radical surgery and 7 patients underwent conservative surgery without special treatment after surgery.Five patients had a history of recurrence,and the fol-low-up time ranged from 1 to 12 years.Conclusion MSBT has special morphology,often bilateral,and is prone to peritoneal implantation and recurrence.It should be distinguished from classical ovarian serous borderline tumor.
2.CD147 regulates the effects of fatty acid synthesis on the proliferation,invasion,and migration of cervical cancer cells via the Akt/mTOR signaling pathway
Jinqiu LI ; Xiangyu SHANG ; Yiran YAN ; Aini AILINUER ; Hasimu AXIANGU
Chinese Journal of Clinical and Experimental Pathology 2024;40(3):261-267
Purpose To investigate the effect of CD147 on the proliferation,invasion and migration of cervical cancer cells and its potential molecular mechanism.Methods The expres-sion data of BSG gene(encoding CD147 protein)in cervical cancer samples were downloaded from UCSC database,and the prognosis of different groups of samples was evaluated by Log-rank test.Western blot was used to detect CD147 expression in the Siha and Hela and H8 cells.The expression of CD147 was downregulated by the lentivirus transfection into Hela cells and its transfection efficiency was verified.Western blot was used to detect the expression of p-Akt,p-mTOR,ACC1,FASN,E-cad-herin and N-cadherin in each group.The content of fatty acids in the cells was detected by BODIPY staining and fatty acid kit.Cell proliferation,invasion and migration were detected by CCK-8,plate cloning and Transwell assay.The cell proliferation,in-vasion and migration ability were detected by plate cloning ex-periment and Transwell test.Results The expression of CD147 in cervical cancer tissues was higher than that in normal cervical tissues(P<0.01).Patients with overexpression of CD147 had poor prognosis.Western blot results showed that compared with H8 cells,the expression of CD147 protein in Siha and Hela cells was increased(P=0.011).After down-regulation of CD147,the protein expression of CD147,ACC1 and FASN in the sh-CD147 group was decreased compared with those in the Hela group(P<0.001).BODIPY fluorescence staining was weak-ened and fatty acid content was decreased(P<0.001).The a-bility of cell colony formation,invasion and migration was de-creased.The expression of E-cadherin protein in sh-CD147 group was increased,and the expression of N-cadherin,p-Akt and p-mTOR was decreased.Compared to sh-CD147,after treatment with Akt agonist SC-79(sh-CD147-SC79),the ex-pression of p-Akt,p-mTOR,ACC1,FASN,N-cadherin in cells was increased,and the expression of E-cadherin was decreased,and the results of lipid staining and fatty acid content were con-sistent with the expression of key enzymes(P<0.01),and the cell proliferation,invasion and migration ability were significant-ly enhanced.Conclusion CD147 through Akt/mTOR signaling pathways regulating the fatty acid synthesis promotes cervical cancer cell proliferation,invasion and migration.
3.Triple negative breast cancer:a study based on histological and immunohistochemical classification
Jing LIAN ; Li HUANG ; Peng BU ; Hong SU ; Yanfeng XI
Chinese Journal of Clinical and Experimental Pathology 2024;40(3):268-273
Purpose To evaluate the classification criteria of triple negative breast cancer(TNBC)based on histomorphol-ogy and immunohistochemistry(IHC),and to provide theoreti-cal basis for the classification and treatment of TNBCs.Methods TNBC subtyping was performed according to the histomorphologi-cal characteristics and the expression of immune markers AR,CD8 and FOXC1,and the clinicopathological features and prog-nostic differences were compared.Results Among 93 cases of TNBC,there were 23 cases(24.7%)of luminal androgen re-ceptor subtypes,24 cases(25.8%)of immunomodulatory type,39 cases(42.0%)of basal immunosuppressive type,and 7 ca-ses(7.5%)of mesenchymal type.There were significant differ-ences in the clinicopathological features of subtypes,including pT stage(P=0.030),histological grade(P<0.001),intersti-tial lymphocyte infiltration pattern(P<0.001),expression of PD-L1(P<0.001),and HER2-low(P=0.024).There was no significant difference in disease-free survival among the sub-types(P>0.05).Univariate survival analysis showed there was significant difference in disease-free survival among the subtypes at pT1 stage(P=0.011),and other clinicopathological features were not independent prognostic factors.Conclusion The clini-copathological characteristics of TNBC subtypes are different,which are expected to be an alternative choice for complex gene expression profile analysis and to provide theoretical basis for subtypic therapy and targeted therapy.
4.Correlation between tumor abnormal protein level and molecular typing and clinicopathological characteristics in breast cancer
Yunting LI ; Xiaotong DONG ; Jianfang GAO ; Yunxiang ZHANG
Chinese Journal of Clinical and Experimental Pathology 2024;40(3):273-278
Purpose To investigate the relationship be-tween the level of tumor abnormal protein(TAP)and the molec-ular subtypes and clinicopathological features of breast cancer,and to analyze the value of TAP in breast cancer screening,di-agnosis and prognosis prediction.Methods The clinical data of 357 breast cancer patients were collected,and the elbow venous blood was collected to detect the TAP condensate area.Immuno-histochemical(IHC)EnVision two-step method was used to de-tect the expression of AR,ER,PR,HER2,p53 and Ki67,and FISH to detect HER2 gene.The relationship between TAP ex-pression and clinicopathological features,molecular subtypes and clinical stages of breast cancer was analyzed,and the rele-vant literature was reviewed.Results Among 357 breast cancer patients,9 cases(2.52%)were TAP negative,36 cases(10.08%)were weakly positive,312 cases(87.40%)were strongly positive,and the positive rate of TAP was 97.48%.AR was positive in 321 cases and negative in 36 cases,ER was pos-itive in 256 cases and negative in 101 cases,PR was positive in 214 cases and negative in 143 cases,HER2 was strongly posi-tive in 98 cases,weakly positive in 214 cases and negative in 45 cases,p53 was positive in 146 cases and negative in 211 cases,Ki67 index was ≥20%in 276 cases and<20%in 81 case.A total of 155 cases of IHC HER2(2+)breast cancer were tested by FISH:140 cases were negative and 15 cases were positive.The expression level of TAP in patients of ≥50 years old expres-sionas significantly higher than that in patients of<50 years old(P<0.05).The expression level of TAP in patients with high Ki67 proliferation index was significantly higher than that in pa-tients with low Ki67 proliferation index(P<0.05).There was a significant difference in TAP expression between patients with different molecular subtypes(P<0.05).Tap expression was higher in triple-negative breast cancer patients than in non-tri-ple-negative breast cancer patients(P<0.05),and it was high-er in Luminal B breast cancer patients than in non-Luminal B breast cancer patients(P<0.05).There was a significant difference in TAP expression between patients with different clin-ical stages(P<0.05),and TAP expression level was positively correlated with clinical stage in breast cancer.Conclusion TAP detection can improve the diagnostic accuracy of breast cancer,and has a certain correlation with the survival rate and prognosis of breast cancer patients.
5.Application of WHO molecular classification in endometrial cancer(2020)and its clinicopathological significance
Liyu CAO ; Zhuangzhuang TIAN ; Lili ZHU ; Zhenzhen BAI ; Cong ZHANG
Chinese Journal of Clinical and Experimental Pathology 2024;40(3):279-284
Purpose To explore the application and clini-copathological significance of molecular classification in endome-trial cancer(EC)of WHO(2020)tumors of the female repro-ductive system.Methods Sixty-two EC patients were collected and categorized into four subgroups,namely POLE mutation type,mismatch repair deficient(MMRd)type,non-specific molecular spectrum(NMSP)type,and p53 mutation type,based on WHO molecular classification tested by PCR and im-munohistochemistry.The correlation among four molecular sub-groups and their clinicopathological features were analyzed.Re-sults The molecular classification was distributed as follows:3(4.8%)cases were POLE-mutated,15(24.2%)cases MMRd,36(58.1%)cases NSMP and 8(12.9%)cases p53 abnormal expression.There were no significant differences a-mong POLE-mutated and infiltration depth,grade,lymph vascu-lar space invasion and other pathological factors such as lymph node metastasis and FIGO stage(P>0.05).Among 15 patients with MMRd,the proportion of FIGO stage Ⅱ+Ⅲ significantly increased.One case showed abnormal overexpression of p53 pro-tein,while two cases showed complete loss of expression in MMRd subgroup.36 cases of NSMP were associated with low histopathological grade(Grade Ⅰ+Ⅱ)(P<0.05),and no significant differences were observed among NSMP and other clinicopathological factors(P>0.05).The p53 abnormal ex-pression in 8 cases was related to high histopathological grade(Grade Ⅲ)(P<0.05),and the rate of lymph node metastasis and FIGO stage Ⅱ+Ⅲ significantly increased in patients with p53 abnormal expression,and although the difference was not statistically significant(P>0.05).Conclusion The molecu-lar subgroups of EC have certain clinical application value,the cases with MMRd and p53 abnormal expression may have poor prognosis than these with POLE-mutated and NSMP.
6.Effect of LPCAT1 on biological behavior of cervical cancer based on β-catenin/Slug signaling pathway
Chunli SHI ; Guihua ZHOU ; Wei CHEN ; Xiaoling WU ; Hong LU ; Chunhua LIN
Chinese Journal of Clinical and Experimental Pathology 2024;40(3):285-290
Purpose To observation the relationship be-tween the β-catenin/Slug signal specific inhibitor FH535 and EMT,and to explore the role of LPCAT1 in regulating the inva-sion,metastasis,and growth of cervical cancer cells.Methods Hela cells were transfected with sh-NC and sh-LPCAT1,and SiHa cells were transfected with Vector group and LPCAT1 over-expression plasmid.SiHa cells were divided into control group(Con),LPCAT1 group,LPCAT1+FH535 group and FH535 group.The proliferation of cervical cancer cells was detected by CCK-8 analysis and colony formation test.The metastasis and invasion ability of cervical cancer cells were detected by wound healing test and Transwell test.Western blot was used to analyze the expression of LPCAT1,β-catenin/Slug signaling pathway and EMT-related proteins in cells.Results Compared with Vector group,the cell viability,colony number,migration and invasion number of SiHa cells in LPCAT1 group increased signif-icantly(P<0.05).Compared with sh-NC group,the cell via-bility,colony number,migration and invasion number of Hela cells in sh-LPCAT1 group decreased significantly(P<0.05).Compared with LPCAT1 group,the levels of Wnt4(1.18±0.05 vs 0.80±0.06),β-catenin(1.05±0.08 vs 0.77±0.05),Slug(1.13±0.06 vs 0.28±0.02),Cyclin D1(0.99±0.06 vs 0.44±0.02),N-cadherin(0.91±0.07 vs 0.46±0.03)and vimentin(0.95±0.06 vs 0.49±0.03)in SiHa cells in LPCAT1+FH535 group decreased significantly(P<0.05),and the level of E-cadherin(0.44±0.03 vs 0.58±0.03)in-creased significantly(P<0.05).In addition,compared with LPCAT1 group,the number of colonies(224±15 vs 146±11),migration(85±3vs51±4)and invasive(166±10 vs 90±5)cells of SiHa cells in LPCAT1+FH535 group decreased signifi-cantly(P<0.05).Conclusion The increase of LPCAT1 ex-pression may promote the metastasis and progress of CC by acti-vating β-catenin/Slug signaling pathway,and LPCAT1 may be a potential marker for predicting CC metastasis.
7.The role and mechanism of MCM5 in the occurrence and development of ovarian cancer
Dong CHEN ; Mingwei ZHANG ; Feifei SUN ; Li LI
Chinese Journal of Clinical and Experimental Pathology 2024;40(3):291-298
Purpose To explore the expression,mechanism and clinical significance of MCM5 in ovarian cancer.Methods The expression of MCM5 mRNA in ovarian cancer and its correlation with patients'survival were analyzed using GEO and TCGA databases.The expression of MCM5 protein in ovarian cancer was detected by immunohistochemistry of SP two-step method,and its relationship with clinicopathological characteris-tics was analyzed.With inhibition of MCM5 by siRNA in ovarian cancer cells.The effects of MCM5 on cell proliferation,migra-tion,invasion,and apoptosis were detected by CCK-8 assay,EDU,plate cloning,Transwell chamber and flow cytometry.Re-sults Immunophenotype:MCM5 does not stain in the fallopian tube epithelium(0/6),with a positivity rate of 48.3%(57/118)in ovarian cancer.The expression of MCM5 in ovarian cancer is significantly higher than in fallopian tube epithelium,showing diffuse strong expression in high-grade serous carcino-ma.MCM5 expression is strongly correlated with ER-negative status and high Ki67 proliferation index.Knocking down MCM5 expression inhibits proliferation(P<0.05),clonogenicity(P<0.05),invasion and migration(P<0.05)of ovarian cancer cells,and promotes apoptosis.Conclusion MCM5 is highly expressed in human ovarian cancer cells and tissues and is asso-ciated with poor prognosis.It is expected to become a new target for the treatment of ovarian cancer.
8.Expression and clinical significance of KIFC1 in endometrioid carcinoma
Tao DENG ; Yuanyuan WEN ; Hui HE ; Liyong QIAN
Chinese Journal of Clinical and Experimental Pathology 2024;40(3):298-302
Purpose The aim of this study is to investigate the relationship between the expression of kinesin family member C1(KIFC1)in endometrioid carcinoma and clinicopathological features and prognosis of endometrioid carcinoma patients.Methods The expression of KIFC1 in 30 cases of paracancer-ous endometrium and 95 cases of endometrioid carcinoma was detected by immunohistochemical SP method.qRT-PCR and Western blot were used to detect the expression level of mRNA and protein of KIFC1 in 30 pairs of fresh cancer tissues and ad-jacent non-cancer tissues.Furthermore,the relationship between KIFC1 protein expression and survival time was analyzed by TC-GA database,and their clinicopathologic features were analyzed.Results The immunohistochemistry results showed the positive rate of KIFC1 in endometrioid carcinoma(61.05%)was signifi-cantly higher than that in the neighboring noncancerous tissue(13.33%),and the difference was statistically significant(P<0.05).The expression of KIFC1 was correlated with myometrial invasion,FIGO stage and lymphatic metastasis(all P<0.05).The relative expression of KIFC1 mRNA in endometrioid carci-noma(2.99±0.59)was significantly higher than that in the neighboring noncancerous tissue(1.00±0.29),and there was significant difference(P<0.05).The relative expression of KIFC1 protein in endometrioid carcinoma(1.70±0.36)was significantly higher than that in the neighboring noncancerous tissue(0.72±0.17),and there was significant difference(P<0.05).Furthermore,elevated KIFC1 expression was positive-ly correlated with a poorer prognosis.Conclusion KIFC1 is upregulated in endometrioid carcinoma and associated with poor prognosis of patients,KIFC1 was expected to be a potential ther-apeutic target and prognostic indicator for endometrioid carcino-ma.
9.High grade B cell lymphoma with concurrent MYC rearrangement and 11q aberrations:a clinicopathological analysis
Susu LU ; Guannan WANG ; Wugan ZHAO ; Dandan ZHANG ; Yanping ZHANG ; Sixia HUANG ; Enjie LIU ; Weiwei WANG ; Lan ZHANG ; Wencai LI
Chinese Journal of Clinical and Experimental Pathology 2024;40(1):24-28
Purpose To investigate the clinicopathological features,molecular genetics and prognosis of high grade B cell lymphoma with concurrent MYC rearrangement and 11q aberra-tions(HGBCL-MYC-11q).MethodsThree cases of HGBCL-MYC-11q were reviewed and analyzed using hematoxylin-eosin staining,immunohistochemistry,EBER in situ hybridization and fluorescence in situ hybridization.Clinical data were collected with follow-up.Results All three patients were male,age was 10,61,and 74 years,respectively.All patients had Ann Arbor stage Ⅳ disease.All three cases were biopsies occurring in the nasopharynx,upper pharynx and ileocecus,respectively.Three cases were morphologically similar to diffuse infiltrative growth of tumor cells,moderate or moderately large cells,round to slightly irregular nuclei and easily visible mitotic figures.Focal necrosis was noted in one case.One case exhibited the distinct"starry sky"pattern.All cases expressed CD20,BCL6 and MUM1 and high Ki67 index,two cases expressed CD10 and two cases ex-pressed BCL2.CD3,CD30 and TDT were all negative.EBER in situ hybridization was all negative.FISH analyses using C-MYC break-apart probes were all positive and all cases had 11q aberrations.One case only had the 11q23.3 amplification;and one case only had the 11q24.3 loss.After a follow-up for 1-18 months,one patient died and two patients survived with disease.ConclusionHGBCL-MYC-11q is rare,morphologically similar to BL/HGBCL,with MYC rearrangement and 11q abnormali-ties.We should enhance awareness of the disease and improve more accurate diagnosis and differential diagnosis of the disease.
10.Clinical pathology and prognostic differences of primary CD5+diffuse large B cell lymphoma
Jialing XIE ; Qing SHI ; Qiyuan BAO ; Lei DONG
Chinese Journal of Clinical and Experimental Pathology 2024;40(1):29-34
Purpose To explore the clinicopathological features and molecular characteristics of primary CD5+diffuse large B cell lymphoma(DLBCL).Methods Immunohisto-chemistry and next-generation sequencing(NGS)were used to compare the pathological features,immunophenotypes,and mo-lecular characteristics between primary CD5+DLBCL and CD5-DLBCL,and to analyze their relationship with prognosis and clinical characteristics of patients.Results Among 311 DLBCL patients,there were 46 cases(14.7%)of CD5+DLBCL.There were no statistically significant differences in patient gen-der,clinical staging,international prognostic index between CD5+DLBCL and CD5-DLBCL,and between CD5+DLBCL with and without MYD88 L265P mutation(P>0.05).Immuno-phenotypically,the overexpression of BCL2(69.5%vs 49.4%,P=0.003)and the co-expression of BCL2 and C-MYC(26%vs 14%,P=0.04)were higher in the CD5+DLBCL group than those in the CD5-DLBCL group;the expression of C-MYC(53%vs 20%),BCL6(93.3%vs 61.3%),Ki67(93.3%vs 64.5%),and co-expression(46.7%vs 20.8%)were higher in the CD5+with MYD88 L265P mutation group than those in the CD5+without MYD88 L265P mutation group(P<0.05).Survival analysis showed that the disease progres-sion-free survival time of patients in the CD5+DLBCL group tended to be shorter than that of patients in the CD5-DLBCL group(P=0.09).Furthermore,the disease progression-free survival time of patients in the CD5+without MYD88 L265P mutation group was significantly longer than that of patients in the CD5+with MYD88 L265P mutation group(P=0.04).NGS detection found differences in the distribution of accompan-ying mutated genes between CD5+DLBCL and CD5-DLBCL groups.ConclusionCD5 expression and CD5+with MYD88 L265P mutation may be potential indicators of poor prognosis in DLBCL patients.

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