Metastatic of CRCC is observed in a third from total patients with clear status of renal cell carcinoma, in which the possibility of CCRCC relapse even after nephtrectomy. Metastatic disease has conventional prognostic factor that predict its prognosis factor such as tumor size, staging and grading, but its utility is currently decreasing. It is of importance to be able to find other means of early detection for metastatic condition in patient with renal cell carcinoma. Cancer development and progression is associated with its tumour microenvironment and its effect on normal cells .
FAP is a marker of activated fibroblasts that is found to be more abundant in tumor with invasive and aggressive phenotype than those in non-invasive and aggressive types. Studies have suggested that with FAP expression is associated with poorer prognosis. Whilst, to detect the effect of malignancy in MCCRC can be seen using TACS grading in which can be assessed by the changes in collage structure; thus, these changes could be used as prediction for invasiveness of MCCRC .
As a multifunctional protein, FAP regulates tumor growth and invasiveness in independent status due to its catalytic activity. From one of its effects, homologous enzyme such as the dipeptidyl-peptidase (DPPIV) may be formed, which facilitates ECM degradation and promotes cancer cell invasion. In addition, both FAP and DPPIV can also act as adhesive molecules, which could interact to integrins and influence the intracellular signal. As a result, an increase in DPPIV level would lead to advanced stage of CCRCC, which indicates association of poor survival rates. From these mechanisms, it is suggested that FAP may have complementary roles in renal carcinogenesis [14, 15].
In this study, we try to describe FAP expression prevalence rate both in stroma and intratumor of mCCRC patient. Other studies have shown that FAP presence in mCCRC patient is correlated with high stage, higher grade and necrotic tumors with 10-years survival. Furthermore, it is found that 96% of all intratumor samples and 84% of all stromal sample in metastatic renal cell carcinoma is found to have positive FAP expression, implying to poorer prognosis among majority of the patients in our center. Our data showed majority of cancer mCCRC patients are positive prevalence of expression for FAP. This finding is in line with other study that found immunostaining FAP is 100% found in patient with sarcomatoid mCCR .
Collagen characteristics in RCC are not well described due to its pattern that has been linked to tumor behavior and clinical factors in other malignancies. In the invasive phase of malignancy, it is found that collagen fibers are aligned perpendicularly to the tumor boundary. These changes have significant differences in both collagen density and fiber alignment between those in grade 1 and grade 4 RCC. This demonstrates that the ability in reorganizing collagen fibers within random collagen matrix is shown by the tumor in order to facilitate the invasion. This ability in organizing a collagen as “a scaffold” may suggest an important step in tumorigenesis. Although this active process has not yet been investigated, it is significant to determine the greatest collagen alignment within the most aggressive of RCCs. However, the current two collagen features cannot be directly used as diagnostic tools since both features lack the applicable discriminant ability [16, 17].
In our investigation, it is found that intratumoral TACS grading was 15% in TACS 1, 32% in TACS 2, and 50% in TACS 50%. Meanwhile, the stromal TACS grading was 11% in TACS 1, 26% in TACS 2, and 46% in TACS 3.
It is found that, FAP status is correlated with TACS grading (r = 0,51 p = 0.001). Via the FAP, finding both in intratumour and stromal lesion can be used as marker for possible metastasis to the other organs. A high TACS grading indicated collagen perpendicular formation, which will inform the occurrence of metastasis.