The Staging Value Of FDG PET/CT And Correlation Between SUV And Proliferation, Invasion, Angiogenesis, Pathology Grading In Esophageal Squamous Carcinoma

Objective To evaluate the correlation between FDG PET standardized uptake value (SUV)of esophageal carcinomas and the expression of Ki-67,MMP-2 and micro-vessel density(MVD),and to determine if SUV value could quantitatively reflect tumor proliferation,invasion and angiogenesis,and to reveal the relationship between SUV and pathological grading of esophageal carcinomas.To evaluate the diagnostic value of FDG PET/CT in classfying TNM staging of esophageal carcinomas by comparing TNM classification by each of the three means of FDG PET/CT,CT and PET with the correspondingly histopathological results.Materials and methods Fourty-seven patients with surgical resected esophageal carcinoma during Jan.2006 to Jan.2008 were enrolled into the present study.Of all the patients,thirty-nine were male,fourteen were female,the median age was 57 years and the age ranged between 39 years and 74 years old.¹⁸F-FDG PET/CT examination was performed one week before operation.All the patients underwent low dose spiral CT and PET scanning from skull base to thigh.CT, PET and PET/CT merged images were obtained from a Xeleris workstation equipped with fusion software.For semi-quantitative analysis,standardized uptake value(SUV) was calculated.Conventional plain CT scan was performed after FDG PET/CT examination to all the patients.Specimens were obtained during surgery and the extention of primary lesions of the tumor.The TNM staging were determined by HE staining,and immunohistochemistry staining of Ki-67,MMP-2 and CD34 was carried out to indicate tumor proliferation,invasion and micro-vessel indensity of esophageal carcinomas.The relationships between FDG SUVmax and Ki67 expression,FDG SUVmax and MMP-2 expression,FDG SUVmax and corresponding MVD were statistically analysed respectively.The AJCC and UICC(2002)protocol were introduced to stage esophageal carcinomas by means of TNM staging and general staging.The length of the tumors was determined by CT and PET/CT,and the results were compared with that of the surgical resected specimen.The correlation between them was analyzed statistically. The TNM staging and general staging of the tumors were determined by CT,PET, and PET/CT respectively,and the results of each of the three modalities were comparing with the histopathological staging as well as being compared with each other.Result Among all the 47 cases,47 specimen were obtained(13 well-differentiated squamous cell tumors,16 moderately differentiated tumors and poorly differentiated tumors).,45 of 47 tumors revealed FDG.accumulation in primary tumor foci confirmed by subsequently histopathologically.The mean FDG SUVmax value was 12.504±6.805.Average Ki-67 index was(7.837±29.798)%,average MMP-2 index was(71.551%±27.126)%and average MVD was(18.429±9.603)accordingly.The SUV and Ki-67 index,MMP-2 index were positively correlated(r=0.581,0.594),and it was not correlated with MVD(P＞0.05).The mean SUV of well-differentiated, moderately differentiated and poorly differentiated tumors were 9.787±1.477, 12.313±0.479,15.053±2.147 respectively,and a significant difference could be determined between them by statistical analysis(P=0.000)Of all the cases,4 were determined to be stageâ… ,15 were determined to be stageâ…¡,19 were determined to be stageâ…¢and 16 were determined to be stageâ…£.Foury-one primary tumors were detected by CT,45 by PET and PET/CT respectively.The tumor length measured by CT,PET/CT and specimen was 6.000±0.943cm,5.210±0.597cm and 4.510±0.989cm respectively.Statistical significance of tumor length could be revealed between CT and surgical resected specimens(P=0.001)and there is no discrepency between PET/CT and resected specimen(P=0.080).As to the relationship between SUV and tumor invasion:There was no statistical discrepencies among T1,T2 and T3 group;however there was statistical discrepancy between T1-T2 group and T4 group and between T3 group and T4 group. SUV was positively correlated to the length of lesion(r=0.777).The accuracy of tumor staging was 46.8%,48.9%,51.1%by CT,PET and PET/CT respectively. Comparison of SUV and histopathologic findings showed that there was no significant between T1-T2 and T3(P＞0.05),and there was significant correlation between T1-T3 and T4(P=0.000).A significant positive correlation was demonstrated between SUV and length of resected specimen.Metastases were detected in local lymphnode in 31 of 47 patients.Histopathological examination revealed metastases in 65 of 387 excised lymphnodes.The mean short-axis of the metastatic lymph nodes was 1.3cm.There were 35 metastatic lymphnodes detected by CT with a mean short-axis of 1.7cm,51 by PET with a mean short-axis of 1.5cm, and 58 by PET/CT with a mean short-axis of 1.7cm.The sensitivity of CT detection of local lymphnodes metastases was 53.8%,the specificity was 93.1%,the diagnostic accuracy was 88.8%;while PET resulted in a sensitivity of 78.5%, specificity of 88.5%,and accuracy of 86.8%;PET/CT resulted in a sensitivity of 89.2%,specificity of 93.7%,accuracy of 93.2%respectively.The accuracy of LN staging in esophageal carcinoma was 74.5%,83.0%and 91.5%by CT,PET and PET/CT respectively.The mean SUV of non-metastatic lymphnodes was 9.427±2.854, and the mean SUV of metastatic lymphnodes was 14.899±3.770.There was significant discrepencies between of them(P=0.000).There were 15 distant metastases in 9 patients detected among all the 47 cases. The accuracy of M staging was 87.2%,93.6%and 95.7%by CT,PET and PET/CT respectively.The accuracy of general staging in esophageal carcinoma was 51.1%, 57.4%and 68.1%by CT,PET and PET/CT respectively.Conclusions A significant positive correlation is demonstrated between FDG PET/CT SUV and Ki-67 index,MMP-2 index of the primary esophageal cancer.SUV could reflect proliferation and invasion potential of tumor.However,there is no significant correlation between SUV and MVD,thus it could not reflect tumor angiogenesis in esophageal cancer.To some extent,SUV could reflect pathologic grading of tumor.PET/CT shows more accurate than both CT and PET in general staging of esophageal carcinomas.PET/CT has more clinical advantages than CT in decteting primary esophageal tumor extent,local lymphnode metastases and distant metastases.However,it has certain limitation in diagnosing primary tumors, especially in the detection of early stage esophageal carcinoma.