DNA aneuploidy is often regarded as an indicator of tumour malignancy. Many early reports have indicated a high frequency of DNA aneuploidy in several human neoplasms. This has inevitably led to detailed investigations of the influence of DNA aneuploidy on cancer invasion and metastatic progression and its potential for predicting prognosis. DNA ploidy reportedly correlates with the myometrial invasion by primary endometrial carcinomas. Aneuploid primary tumours also recur more frequently as compared with diploid tumours (Giovagnoli et al., 1995). Sun el al. (1993a) found DNA ploidy to be a very important and independent prognostic indicator in patients with stage A-C colonic adenocarcinomas. The survival of patients with prostatic adenocarcinoma has also been correlated with DNA ploidy (Azua et al., 1996). Yuan el al. (1992) had reported some years ago that DNA ploidy was significantly predictive of relapse of disease as well as overall survival in a series of patients with node-negative breast cancer. Azua et al. (1997) measured the DNA ploidy in fine-needle aspirates (FNAs) of breast cancer patients. They found DNA quantification to be significantly related to survival times. In another study involving a large series of breast cancer, Gilchrist et al. (1993) found that DNA ploidy strongly correlated with lymph node metastasis and early death. DNA ploidy correlated with the presence of tumour in the axillary lymph nodes, sometimes with distal metastases in a small series of breast cancer (Sherbet and Lakshmi, 1997). In a study of gastric cancers, Baba et al. (2002) noticed that DNA aneuploidy correlated with high invasive and metastatic potential and with poor prognosis. Ioakim-Liossi et al. (2000) investigated a series of superficial transitional cell bladder carcinomas. It may be recalled that a proportion of superficial tumours recur as invasive tumours. In this context it is of much interest to note that Ioakim-Liossi et al (2000) found a highly significant correlation between DNA aneuploidy and tumour recurrence.
Contrary to this, pancreatic carcinomas with diploid DNA content are said to be less aggressive than corresponding aneuploid ones. Furthermore, patients with diploid tumours have shown decreased median survival (Linder et al, 1995; Southern et al., 1996). Similar findings have also been reported in respect of colorectal cancer (Sampedro et al., 1996) and hepatocellular carcinoma (Bottger et al., 1996). Esteva et al. (2001) found no relationship between DNA ploidy and prognosis in lung cancer, although others, e.g. Cibas et al. (1989), had previously reported such a relationship. Similarly, neither overall survival nor disease-free survival of patients with head and neck cancers correlated with DNA ploidy (Tamas et al., 1999). Igarashi et al. (1999) noticed no changes in the state of DNA ploidy in the progression of early gastric cancer to advanced stages of the disease. Thus, overall, there is little consensus concerning the value of DNA ploidy as a prognostic marker (Camplejohn et al., 1993; Hedley et al., 1993; Wenger et al., 1993).
It should also be noted here that hyperdiploidy has been associated with good prognosis and haploid state with poor outlook in childhood leukaemia (Salford et al, 1996; Harrison, 2000; also see IHN Wong et al, 2000). Presumably, it is not merely the relationship between the general state of chromosome number or DNA ploidy to disease progression that one needs to take into account, but more importantly whether individual genes or cohorts of genes are amplified into multiple copies. It is not reasonable to assume that the chromosomal complement is amplified as a whole. But it is possible that specific chromosomes might be increased in number with each abnormal cell proliferation cycle. Abnormal cell cycle progression leads to hyperdiploidy. Thus we know that over-expression of both cyclin D3 and p2iwafl/c»P1, itself subject to regulation by cyclin D3 and p53, is associated with enhanced ploidy (Kikuchi et al, 1997; Zimmet and Ravid, 2000). Non-random alterations of chromosomes occur at a high level in hypodiploid AML and indicate poor survival. This is in sharp contrast with hyperdiploid AML, which has low non-random chromosomal changes and good prognosis (Ramos et al, 2000). ALL patients with trisomy of chromosomes 10, 17 and 18 have better prognosis than those without trisomy. Trisomy of chromosome 5 is associated with worse prognosis (Heerema et al, 2000). Aneuploidy has been reported to correlate with the expression of aberrant markers in both AML and ALL. Eksioglu-Demiralp et al (1999) described a series of 61 AML and ALL patients of whom 18 were aneuploid and aberrant markers were expressed in 20 patients. Seven (of 18) patients who expressed abnormal markers had aneuploid DNA content, and had short survival of three months. It is inconceivable that aneuploidy should be studied on its own merit for its relevance to prognosis of leukaemia, especially without reference to the S-phase fraction (SPF). The latter could be an important parameter to include in these studies and indeed might be an important prognostic factor (Kute et al., 1995). Hyperdiploid ALL is more sensitive to antimetabolite therapy (Kaspers et al., 1995), and this could be due to high SPF attendant upon the hyperdiploid state. Presumably for the same reason hypodiploid multiple myeloma is refractory to chemotherapy.
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