目的探讨伴破骨样巨细胞的胰腺未分化癌(undifferentiated carcinoma with osteoclast-like giant cells of the pancreas,UCOGCP)的临床病理学特征。方法回顾性分析5例UCOGCP的临床病理学特征、免疫表型及分子特征。采用免疫组化、ARMS...目的探讨伴破骨样巨细胞的胰腺未分化癌(undifferentiated carcinoma with osteoclast-like giant cells of the pancreas,UCOGCP)的临床病理学特征。方法回顾性分析5例UCOGCP的临床病理学特征、免疫表型及分子特征。采用免疫组化、ARMS-PCR(amplification refractory mutation system-polymerase chain reaction)技术检测UCOGCP的免疫组化及分子特征。结果5例UCOGCP患者中男性3例,女性2例,平均年龄55.6岁,其中4例为手术切除标本,1例为EUS-FNA标本;眼观:肿瘤最大径5.5~8.0 cm,切面灰黄色,实性质硬,局部可见坏死样物,部分病例可见白色骨样物质沉积。镜检:肿瘤细胞通常在出血或坏死区域附近,细胞黏附性差。肿瘤细胞包括三类:肿瘤性单核细胞、非肿瘤性的卵圆形或梭形单核组织细胞及破骨样巨细胞,细胞混杂分布,部分病例可见骨样基质,病理性核分裂象多见,2例合并有导管腺癌成分,1例可见神经侵犯,1例门静脉内可见癌栓,3例发生肝脏转移。免疫表型:5例单核组织细胞及破骨样巨细胞vimentin、CD68均阳性;CK(AE1/AE3)、CK7、EMA为局灶阳性(4/5);HMB-45、SMA、desmin、S-100、SOX10、SS18-SSX、HMB-45、Myogenin均阴性;Ki67增殖指数为20%~50%。其中1例进行了KRAS、NRAS、BRAF基因及TERT启动子突变检测,检测到KRAS G12D位点突变,未检测到NRAS、BRAF及TERT启动子区突变。结论UCOGCP相对较少见,此类型肿瘤的临床行为尚无法准确预测,需要积累更多病例准确了解其生物学行为。展开更多
BACKGROUND Hypoxia in oral cancer promotes tumoral invasion by inducing epithelial-mesenchymal transition,leading to aggressive tumor progression.AIM To characterize the expression of hypoxia-inducible factor 1-alpha(...BACKGROUND Hypoxia in oral cancer promotes tumoral invasion by inducing epithelial-mesenchymal transition,leading to aggressive tumor progression.AIM To characterize the expression of hypoxia-inducible factor 1-alpha(HIF-1α)at the invasive tumor front(ITF)in comparison to tumor islands(TI)in oral squamous cell carcinoma(OSCC)and to explore its relationship with E-cadherin and Vimentin expression.METHODS Thirty-eight cases of OSCC and five cases of normal oral mucosa(NOM)were included in this study.The ITF was identified based on the region and immune expression of AE1/AE3.Immunohistochemistry was performed to assess the expression of HIF-1α,Vimentin,and E-cadherin.The immunostaining was analyzed using an immunoreactive score,and the results were illustrated using immunofluorescence.RESULTS HIF-1αexpression was significantly higher in the TI region compared to the ITF region(P=0.0134).Additionally,a significant difference was observed between TI and NOM(P=0.0115).In the ITF regions,HIF-1αexpression showed a significant correlation with Vimentin expression,with higher levels of HIF-1αassociated with increased Vimentin expression(P=0.017).CONCLUSION Based on the results of this study,HIF-1αappears to play a distinct role in OSCC tumor progression,underscoring the importance of exploring hypoxia-driven changes in cellular phenotype at the ITF of OSCC.Further research is needed to better understand their impact on OSCC prognosis.展开更多
Various genetic association studies have identified numerous single nucleotide polymorphisms(SNPs)associated with nasopharyngeal carcinoma(NPC)risk.However,these studies have predominantly focused on common variants,l...Various genetic association studies have identified numerous single nucleotide polymorphisms(SNPs)associated with nasopharyngeal carcinoma(NPC)risk.However,these studies have predominantly focused on common variants,leaving the contribution of rare variants to the“missing heritability”largely unexplored.Here,we integrate genotyping data from 3925 NPC cases and 15,048 healthy controls to identify a rare SNP,rs141121474,resulting in a Glu510Lys mutation in KLHDC4 gene linked to increased NPC risk.Subsequent analyses reveal that KLHDC4 is highly expressed in NPC and correlates with poorer prognosis.Functional characterizations demonstrate that KLHDC4 acts as an oncogene in NPC cells,enhancing their migratory and metastatic capabilities,with these effects being further augmented by the Glu510Lys mutation.Mechanistically,the Glu510Lys mutant exhibits increased interaction with Vimentin compared to the wild-type KLHDC4(KLHDC4-WT),leading to elevated Vimentin protein stability and modulation of the epithelial-mesenchymal transition process,thereby promoting tumor metastasis.Moreover,Vimentin knockdown significantly mitigates the oncogenic effects induced by overexpression of both KLHDC4-WT and the Glu510Lys variant.Collectively,our findings highlight the critical role of the rare KLHDC4 variant rs141121474 in NPC progression and propose its potential as a diagnostic and therapeutic target for NPC patients.展开更多
基金Supported by Comisión Sectorial de Investigación Científica(CSIC-Research Group 88180)The Agencia Nacional de Investigación e Innovación/Sistema Nacional de Investigadores(ANII/SNI)The Programa de Desarrollo de las Ciencias Básicas(PEDECIBA),Uruguay.
文摘BACKGROUND Hypoxia in oral cancer promotes tumoral invasion by inducing epithelial-mesenchymal transition,leading to aggressive tumor progression.AIM To characterize the expression of hypoxia-inducible factor 1-alpha(HIF-1α)at the invasive tumor front(ITF)in comparison to tumor islands(TI)in oral squamous cell carcinoma(OSCC)and to explore its relationship with E-cadherin and Vimentin expression.METHODS Thirty-eight cases of OSCC and five cases of normal oral mucosa(NOM)were included in this study.The ITF was identified based on the region and immune expression of AE1/AE3.Immunohistochemistry was performed to assess the expression of HIF-1α,Vimentin,and E-cadherin.The immunostaining was analyzed using an immunoreactive score,and the results were illustrated using immunofluorescence.RESULTS HIF-1αexpression was significantly higher in the TI region compared to the ITF region(P=0.0134).Additionally,a significant difference was observed between TI and NOM(P=0.0115).In the ITF regions,HIF-1αexpression showed a significant correlation with Vimentin expression,with higher levels of HIF-1αassociated with increased Vimentin expression(P=0.017).CONCLUSION Based on the results of this study,HIF-1αappears to play a distinct role in OSCC tumor progression,underscoring the importance of exploring hypoxia-driven changes in cellular phenotype at the ITF of OSCC.Further research is needed to better understand their impact on OSCC prognosis.
基金supported by the National Natural Science Foundation(82261160657,82102490,and 81572781)the Guangdong Basic and Applied Basic Research Foundation(2024A1515013061)+2 种基金the Sci-Tech Project Foundation of Guangzhou City(2023A04J2141)Chang Jiang Scholars Program(J.-X.B.)the Hong Kong Research Grant Council(RGC)Theme-based Research Scheme Funds(T12-703/22-R and T12-703/23-N).
文摘Various genetic association studies have identified numerous single nucleotide polymorphisms(SNPs)associated with nasopharyngeal carcinoma(NPC)risk.However,these studies have predominantly focused on common variants,leaving the contribution of rare variants to the“missing heritability”largely unexplored.Here,we integrate genotyping data from 3925 NPC cases and 15,048 healthy controls to identify a rare SNP,rs141121474,resulting in a Glu510Lys mutation in KLHDC4 gene linked to increased NPC risk.Subsequent analyses reveal that KLHDC4 is highly expressed in NPC and correlates with poorer prognosis.Functional characterizations demonstrate that KLHDC4 acts as an oncogene in NPC cells,enhancing their migratory and metastatic capabilities,with these effects being further augmented by the Glu510Lys mutation.Mechanistically,the Glu510Lys mutant exhibits increased interaction with Vimentin compared to the wild-type KLHDC4(KLHDC4-WT),leading to elevated Vimentin protein stability and modulation of the epithelial-mesenchymal transition process,thereby promoting tumor metastasis.Moreover,Vimentin knockdown significantly mitigates the oncogenic effects induced by overexpression of both KLHDC4-WT and the Glu510Lys variant.Collectively,our findings highlight the critical role of the rare KLHDC4 variant rs141121474 in NPC progression and propose its potential as a diagnostic and therapeutic target for NPC patients.
