Biomarkers vs conventional histological analysis to detect lymph node micrometastases in bladder cancer: a real improvement?

OBJECTIVE

To improve the sensitivity of histological examination in detecting occult lymph node (LN) dissemination of bladder cancer using gene expression analysis.

PATIENTS AND METHODS

We carried out a retrospective study that included 504 formalin-fixed paraffin-embedded LNs from 90 patients with muscle invasive bladder cancer and 35 controls.

Gene expression values of two molecular biomarkers (FXYD3 and KRT20) were analysed using reverse transcription real-time quantitative PCR (RT-qPCR).

Molecular results were compared with histological status and patients' clinical outcomes.

RESULTS

Of the 90 patients analysed, 16 were positive and 74 were negative by histological analysis. Of these 74, 19 were classified as positive using RT-qPCR.

Significant differences in cancer-specific (P = 0.011) and recurrence-free (P = 0.009) survival were found between the three patient groups (patients positive by both techniques, patients negative by both techniques, and patients negative by histological but positive by molecular analysis).

A significant difference was not found between histologically negative but molecularly positive patients and patients who were negative by both techniques, but a clear trend to a worse outcome was found in those patients who became node-positive after molecular analysis.

CONCLUSIONS

The analysis of FXYD3 and KRT20 could improve current pathological examination for the detection of micrometastases in LNs.

Further and more extensive studies will determine the real prognostic value of such LN micrometastases.