Associations between ADC histogram analysis values and tumor-micro milieu in uterine cervical cancer

The complex interactions of the tumor micromilieu may be reflected by diffusion-weighted imaging (DWI) derived from the magnetic resonance imaging (MRI). The present study investigated the association between apparent diffusion coefficient (ADC) values and histopathologic features in uterine cervical cancer.

In this retrospective study, prebiopsy MRI was used to analyze histogram ADC-parameters. The biopsy specimens were stained for Ki-67, E-cadherin, vimentin and tumor-infiltrating lymphocytes (TIL, all CD45 positive cells). Tumor-stroma ratio (TSR) was calculated on routine H&E specimens. Spearman's correlation analysis and receiver-operating characteristics curves were used as statistical analyses.

The patient sample comprised 70 female patients (age range 32-79 years; mean age 55.4 years) with squamous cell cervical carcinoma. The interreader agreement was high ranging from intraclass coefficient (ICC) = 0.71 for entropy to ICC = 0.96 for ADCmedian. Several ADC-histogram parameters correlated strongly with the TSR. The highest correlation coefficient achieved p10 (r = -0.81, p < 0.0001). ADCmean can predict tumors with high TSR, AUC: 0.91, sensitivity: 0.91 (95% CI 0.77;0.96), specificity: 0.91 (95% CI 0.78;0.97). Several ADC-histogram parameters correlated slightly with the proliferation index Ki-67. No associations were found with TIL, E-Cadherin and vimentin. In well and moderately differentiated cancers, ADC histogram values showed stronger correlations with Ki-67 and TSR than in poorly differentiated tumors.

ADC values are strongly associated with tumor-stroma ratio. The ADC mean can be used to predict tumors with high TSR. Associations between histopathology and ADC values depend on tumor differentiation. ADC values show only weak associations with Ki-67 and none with TIL, vimentin and E-cadherin.