Usually, the UTUC diagnosis is easy, but it occurred sometimes that the UTUC could be misdiagnosed as renal carcinoma, or NTHN. In this study, there were 3 cases (5%) which were diagnosed as renal carcinoma. They accepted the radical nephrectomy instead of classic surgical therapy for UTUC, radical nephrectourectomy. For them, the prognosis was obviously different. And for the UTUC patients, the progression like recurrence and metastasis are not easily detected or definite diagnosed, even through an imaging examination. So it is needed some simple indicators to differentiate UTUC with other upper urinary tract diseases and to reveal the development of UTUC and curative effect.
Although some indicators like CxBladder monitor, UroVysion, NMP-22 and bladder tumor antigen were used in diagnosis and monitoring of TCC, few biomarkers achieve high sensitivity and specificity. And only a few established prognostic factors were found to effectively assess the tumor progression of UTUC. The expensive and time-consuming nature also restricted new methods’ developments. Upon these, there is no clinical recognized bio-indicator for diagnosis, differential diagnosis and status assessment of UTUC.
The classic serum tumor makers (CSTMs, including CA242, CA199, CA125, CEA, AFP, SCC and CA724) are the most commonly used indicators for predicting and monitoring the residual and recurrent of tumors. SCC were used for squamous cell carcinoma predicting[12, 13], all other CSTMs were related with digestive system cancer or reproductive cancer[10, 14–18]. However, some unconventional roles were played in CSTMs: CEA and SCC were used for lung cancer diagnosis and prognosis[19, 20]; CA125 and CA199 was reported as significant markers of endometrium pathology; SCC had a fair diagnostic value for hepatocellular carcinoma. These meant that CSTMs might have more unique values for diagnosis and prognosis of cancerous diseases. However, among these 7 CSTMs, only CEA had been reported as early sign of malignancy in urotheliomas of the upper urinary tract and closely related to the recurrence and survival[23, 24].
In our study, we found that the value or AR in the most of the single CSTMs and the NAC in CSTMs group were significantly augmented in UTUC than in RCCC, NTHN and RCCC + NTHN, which may help to differentiate the UTUC with other upper urinary tract common diseases, malignant or benign. This also suggested the potential compliant relationship between CSTMs and UTUC. The postop CSTMs parameters were significantly lower than the preop ones and have re-augmented in postop PD patients. This revealed that the changes of group of CSTMs complied with the changes of UTUC disease. For the differential diagnosis, CEA and CA724 presented the best ability, but for the disease assessment, CA242 had a best behavior. So it revealed that the single CSTMs could not sacrifice the both functions.
According to the results in all these comparisons, here we have got 6 CSTMs: CA242, CA199, CEA, AFP, SCC and CA724, which were related with UTUC. A test strategy based on these 6 CSTMs was recommended in the clinical detection. The relationship between this strategy and differential diagnosis and assessment of UTUC was re-check in the comparisons above, the P values were almost the lowest and the positive results covered all the comparisons. So the recommended strategy was considered practical, and the AR seemed to be more important than the value.
In pathological level, tumor load, grade, invasive depth, seemed like no significant relationship with most of the single CSTMs, the same to grade and invasive depth with CSTMs group. The NAC on CSTMs by the recommended strategy was linear correlated with tumor load. All these meant that the CSTMs were related with tumor cell quantity, the CSTMs were produced by tumor cell since perhaps the beginning, and the NAC on CSTMs might be a good indicator to assess the changes of disease.
The immunohistochemical labelling results confirmed the fact that the UTUC tissues, but not the paracancerous tissues, significantly contained the CSTMs, at least CA199, CA125, CEA, AFP and CA724. In which, CA199 and CEA were strongly expressed, while CA125 was expressed with very small amount (but also much more strongly than paracancerous tissues). These results were highly in accord with the previous biochemical results and the recommended strategy based on the biochemical results. According to these all above, the CSTMs were specially secreted by the UTUC cell, and the recommended test strategy was practical. This explained the compliance of the CSTMs changes with UTUC disease changes.