Abstract
To address the value of qRT-PCR and IHC in accurately detecting lymph node micrometastasis in gynecological cancer, we performed a systematic approach, using a set of dual molecular tumor-specific markers such as cytokeratin 19 (CK19) and carbonic anhydrase 9 (CA9), in a series of 46 patients (19 with cervical cancer, 18 with endometrial cancer, and 9 with vulvar cancer). A total of 1281 lymph nodes were analyzed and 28 were found positive by histopathology. Following this documentation, 82 lymph nodes, 11 positive and 71 negative, were randomly selected and further analyzed both by IHC and qRT-PCR for CK19 and CA9 expression. All 11 (100%) expressed CK19 by IHC, while only 6 (54.5%) expressed CA9. On the contrary, all the histologically negative for micrometastases lymph nodes were also negative by IHC analysis for both markers. The comparative diagnostic efficacy of the two markers using qRT-PCR, however, disclosed that the analysis of the same aliquots of the 82 lymph nodes led to 100% specificity for the CK19 biomarker, while, in contrast, CA9 failed to recapitulate a similar pattern. These data suggest that qRT-PCR exhibits a better diagnostic accuracy compared to IHC, while CK19 displays a consistent pattern of detection compared to CA9.
Highlights
A considerable percentage of women with gynecological cancer associated with histologically negative lymph nodes develop relapse
We performed a comprehensive analysis for the assessment of the specificity and validity of the two major approaches, that is, IHC and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), currently utilised for the detection of micrometastases in gynecological cancer
Our approach was based on the simultaneous evaluation of the diagnostic capacity and sensitivity of specific epithelial markers, such as cytokeratin 19 (CK19) and carbonic anhydrase 9 (CA9), which are constitutively expressed in cervical, endometrial and vulvar cancer, but not in normal lymph nodes [29]
Summary
A considerable percentage of women with gynecological cancer associated with histologically negative lymph nodes develop relapse. This important clinical issue has led to further investigations on the putative factors that can lead to this particular biological behavior [1]. Several studies on the evaluation of patients with melanoma [2] or breast cancer [3] suggested as a potential cause of relapse, the presence of micrometastasis, defined as tumor deposits measuring 0.2– 2 mm in apparently negative lymph nodes [4]. Its importance at the time of surgery is underscored by the significant effects on the five-year survival rates. Further technical advancements employing several aspects of laparoscopy have significantly improved its utility and BioMed Research International resulted in the development of new techniques, such as laparoscopic-assisted radical vaginal hysterectomy [5] and radical vaginal trachelectomy [6]
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