In vivo Aneuploidization during the Expansion of Renal Adenocarcinoma

Abstract

Background/Aims: A correlation has been observed between DNA ploidy and other prognostic parameters such as tumor stage and grade. The present study evaluates tumor aneuploidization during renal adenocarcinoma expansion and growth. Methods: A total of 252 renal tumors were analyzed between 1969 and 2001. Evaluated variables were age, TNM, Fuhrman classification, histology, size and DNA. A tumor was homogeneous when all the samples were diploid or aneuploid, and a heterogeneous tumor was the coexistence of aneuploid and diploid samples, or all-aneuploid with different aneuploid clones. Results: A total of 224 tumors were included (coefficient of variation <8). The DNA study classified 129 (57.6%) as diploid and 95 (42.4%) as aneuploid. The percentage of aneuploid tumors increased significantly with the pathological stage. Both aneuploid patterns were also significantly more frequent in advanced pathological stages. Tumors with multiple aneuploid clones (n = 17) were significantly more frequent in tumors measuring `4 cm. Both aneuploid patterns showed no differences in survival (p = 0.83), indicating that the heterogeneous pattern probably represents an intermediate step between diploid and homogeneous aneuploid tumor status. Conclusions: The aneuploid pattern is more common in more advanced stages of the disease, with no clear correlation to primary tumor size. This suggests gradual aneuploidization with tumor expansion and growth.

Single-chromosome Gains Commonly Function as Tumor Suppressors

“…To accomplish this, we took advantage of naturally occurring Robertsonian translocations to generate mouse embryonic fibroblasts (MEFs) trisomic for chromosome 1, 13, 16, or 19, as well as sibling-matched euploid controls (Williams et al, 2008). While advanced malignancies frequently harbor complex karyotypes that include multiple chromosome gains and/or losses, early-stage cancers typically exhibit one or a few arm-length or whole-chromosome aneuploidies (Balaban et al, 1986; Di Capua Sacoto et al, 2011; Lai et al, 2007; Magnani et al, 1994; El-Rifai et al, 2000). Thus, these trisomies likely recapitulate the karyotypic state of pre-malignant or early-stage cancer lesions, and their study can shed light on the role of aneuploidy in cancer development and evolution.…”

“…First, our study has primarily focused upon the consequences of single-chromosome trisomies and tetrasomies. This degree of aneuploidy is frequently observed in early-stage lesions in a variety of tumor types (Balaban et al, 1986; Di Capua Sacoto et al, 2011; Lai et al, 2007; Magnani et al, 1994; El-Rifai et al, 2000). It could be the case that these low levels of aneuploidy are in fact tumor protective, while complex karyotypes or the multiple chromosome gains found in more advanced malignancies are tumor promoting.…”

Prognostic Nomogram for Disease-Free Survival in Patients with Renal Adenocarcinoma

“…Several studies have demonstrated similar results regarding the independent prognostic value of DNA ploidy for survival and tumor progression [12,13] .…”

“…Fuhrman et al [11] have demonstrated that nuclear grade is better than other prognostic variables in predicting the development of metastasis after nephrectomy in RA. However, in many studies (including this study), nuclear grade achieved independent prognostic value for survival only when grouped in two or three categories [12][13][14] . Only a few studies with larger sample sizes have demonstrated the prognostic value of the nuclear grade when considering its four categories [15,16] .…”

“…Our nomogram was developed using postoperative data, including a variable (DNA ploidy) whose prognostic value has been demonstrated in several studies [12,13] . The main utility of a postoperative nomogram is its possibility to classify patients into groups that are more or less likely to suffer disease relapse.…”