90例结直肠癌中前列腺特异性膜抗原的表达研究
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摘要
目的:探讨结直肠癌(colorectal cancer,CRC)患者中前列腺特异性膜抗原(prostate-specific membrane antigen,PSMA)的表达及临床病理影响因素。方法:选取90例CRC患者的组织切片,应用免疫组织化学检测癌组织和癌旁正常组织的PSMA、血管标志蛋白CD31的表达水平,并对PSMA的表达水平与CRC临床病理因素的关系进行分析。结果:PSMA在正常结直肠组织中免疫组织化学染色为阴性,在CRC组织中有较高比例免疫组织化学染色。但染色阳性部位不在肿瘤细胞,而是在肿瘤新生血管内皮细胞,总染色率为76.7%。PSMA染色评分在不同年龄及组织学类型中具有显著性差异,高年龄组(≥60岁)及普通型腺癌组的PSMA染色评分更高(P<0.05)。结论:PSMA在90例CRC患者中高比例表达,表达部位为肿瘤新生血管内皮细胞,与部分临床病理因素有关,可能成为CRC诊断及治疗的特异性标志物。
Objective: To explore the expression of prostate-specific membrane antigen(PSMA) and its correlation with the clinicopathological parameters of colorectal cancer(CRC) patients. Methods: Immunohistochemistry was used to examine the expression of PSMA in colorectal cancer and adjacent normal tissues obtained from 90 patients from Alenabio company, Xi'an, China. CD31 staining was also performed as a reference. The correlation between PSMA expression and clinicopathological parameters was analyzed. Results: The expression of PSMA was absent in the adjacent normal colorectal tissues. However, a high PSMA staining rate(76.7%) was observed in colorectal cancer tissues. Moreover, PSMA staining was not observed in cancer cells, but in tumor-associated neo-vasculature. The statistical analysis showed that the PSMA staining scores were significantly different based on the age and histological type.The PSMA staining scores in the elderly group(≥60 years old) and the common adenocarcinoma group were higher(P<0.05). Conclusions: The percentage of PSMA-positive colorectal cancer cells in the 90 CRC patients was high and PSMA was mainly expressed in the endothelial cells of tumor-associated neo-vasculature. Thus, PSMA could be a potential biomarker for the diagnosis and treatment of colorectal cancer.
Objective: To explore the expression of prostate-specific membrane antigen(PSMA) and its correlation with the clinicopathological parameters of colorectal cancer(CRC) patients. Methods: Immunohistochemistry was used to examine the expression of PSMA in colorectal cancer and adjacent normal tissues obtained from 90 patients from Alenabio company, Xi'an, China. CD31 staining was also performed as a reference. The correlation between PSMA expression and clinicopathological parameters was analyzed. Results: The expression of PSMA was absent in the adjacent normal colorectal tissues. However, a high PSMA staining rate(76.7%) was observed in colorectal cancer tissues. Moreover, PSMA staining was not observed in cancer cells, but in tumor-associated neo-vasculature. The statistical analysis showed that the PSMA staining scores were significantly different based on the age and histological type.The PSMA staining scores in the elderly group(≥60 years old) and the common adenocarcinoma group were higher(P<0.05). Conclusions: The percentage of PSMA-positive colorectal cancer cells in the 90 CRC patients was high and PSMA was mainly expressed in the endothelial cells of tumor-associated neo-vasculature. Thus, PSMA could be a potential biomarker for the diagnosis and treatment of colorectal cancer.
引文
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[25]Boegemann M,Schrader AJ,Rahbar K.177Lu-PSMA therapy:Current evidence for use in the treatment of patients with metastatic prostate cancer[J].Urologe A,2017,56(11):1440-1444.
[2]Chen W,Zheng R,He J,et al.Cancer Statistics in China,2015[J].CA Cancer J Clin,2016,66(2):115-132.
[3]West NP,Kobayashi H,Takahashi K,et al.Understanding optimal colonic cancer surgery:comparison of Japanese D3 resection and European complete mesocolic excision with central vascular ligation[J].J Clin Oncol,2012,30(15):1763-1769.
[4]Stone L.Imaging:Predicting 68Ga-PSMA-PET-CT positivity for recurrent disease[J].Nat Rev Urol,2018,15(3):137.
[5]Verburg FA,Pfestroff A.Imaging:PSMA PET-CT in initial prostate cancer staging[J].Nat Rev Urol,2016,13(9):498-499.
[6]Maurer T,Eiber M,Schwaiger M,et al.Current use of PSMA-PET in prostate cancer management[J].Nat Rev Urol,2016,13(4):226-235.
[7]Ghosh A,Heston WD.Tumor target prostate specific membrane antigen(PSMA)and its regulation in prostate cancer[J].J Cell Biochem,2004,91(3):528-539.
[8]Chang SS,Reuter VE,Heston WD,et al.Five different anti-prostatespecific membrane antigen(PSMA)antibodies confirm PSMA expression in tumor-associated neovasculature[J].Cancer Res,1999,59(13):3192-3198.
[9]Haffner MC,Laimer J,Chaux A,et al.High expression of prostatespecific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity[J].Mod Pathol,2012,25(8):1079-1085.
[10]Silver DA,Pellicer I,Fair WR,et al.Prostate-specific membrane antigen expression in normal and malignant human tissues[J].Clin Cancer Res,1997,3(1):81-85.
[11]Haffner MC,Kronberger IE,Ross JS,et al.Prostate-specific membrane an-tigen expression in the neovasculature of gastric and colorectal cancers[J].Hum Pathol,2009,40(12):1754-1761
[12]Yang X,Mease RC,Pullambhatla M,et al.[(18)F]fluorobenzoyllysinepentanedioic acid carbamates:new scaffolds for positron emission tomography(PET)imaging of prostate-specific membrane antigen(PSMA)[J].J Med Chem,2016,59(1):206-218.
[13]Kiess AP,Banerjee SR,Mease RC,et al.Prostate-specific membrane antigen as a target for cancer imaging and therapy[J].Q J Nucl Med Mol Imaging,2015,59(3):241-268.
[14]Salas RF,Amir T,Sheikhbahaei S,et al.Imaging of Non-Prostate Cancers Using PSMA-Targeted Radiotracers:Rationale,Current State of the Field,and a Call to Arms[J].J Clin Oncol,2018[Epub ahead of print].
[15]Gorin MA,Rowe SP.Kidney cancer:PSMA:a potential therapeutic target in RCC[J].Nat Rev Urol,2017,14(11):646-647.
[16]Abdel-Hadi M,Ismail Y,Younis L.Prostate-specific membrane antigen(PSMA)immunoexpression in the neovasculature of colorectal carcinoma in Egyptian patients[J].Pathol Res Pract,2014,210(11):759-763.
[17]Milowsky MI,Nanus DM,Kostakoglu L,et al.Vascular targeted therapy with antiprostate-specific membrane antigen monoclonal antibody J591 in advanced solid tumors[J].J Clin Oncol,2007,25(5):540-547.
[18]Pandit-Taskar N,O'Donoghue JA,Divgi CR,et al.Indium 111-labeled J591 anti-PSMA antibody for vascular targeted imaging in progressive solid tumors[J].EJNMMI Res,2015,5(1):28.
[19]Huang YT,Fong W,Thomas P.Rectal Carcinoma on 68Ga-PSMA PET/CT[J].Clin Nucl Med,2016,41(3):e167-e168.
[20]Hangaard L,Jochumsen MR,Vendelbo MH,et al.Metastases from colorectal cancer avid on 68Ga-PSMA PET/CT[J].Clin Nucl Med,2017,42(7):532-533.
[21]Stoykow C,Huber-Schumacher S,Almanasreh N,et al.Strong PSMA radioligand uptake by rectal carcinoma:who put the"S"in PSMA[J]?Clin Nucl Med,2017,42(3):225-226.
[22]张小龙,高枫,陈利生,等.结直肠癌病理组织学类型分析[J].广西医学,2008,30(11):1671-1672.
[23]Secco GB,Fardelli R,Campora E,et al.Primary mucinous adenocarcinomas and signet-ring cell carcinomas of colon and rectum[J].Oncology,1994,51(1):30.
[24]Baum RP,Kulkarni HR,Schuchardt C,et al.177Lu-Labeled prostatespecific membrane antigen radioligand therapy of metastatic castration-resistant prostate cancer:safety and efficacy[J].J Nucl Med,2016,57(6):1006-1013.
[25]Boegemann M,Schrader AJ,Rahbar K.177Lu-PSMA therapy:Current evidence for use in the treatment of patients with metastatic prostate cancer[J].Urologe A,2017,56(11):1440-1444.