Case report
A 74-year-old man had undergone radical cystectomy in September 1992 for a high-grade, invasive and multiple TCC of the urinary bladder (G2/pT2) and had an ileal neobladder constructed. He was a heavy smoker (600 packs per year) and had previously been healthy. There was no family history of malignancy.
A cytogen-etic study of the tumour cells in culture showed many structural and numeric non-clonal abnormalities. Furthermore, a cytogenetic study of lymphocytes showed no clonal disturbances, but structural abnormalities in 13% of the metaphase stages and 3.5% with chromosomal weakness, both values being greater than normal. Because of the chromosomal abnormalities the patient was followed closely; a year later he presented with melanoma and was diagnosed with a second epithelial cancer in the sigmoid colon. An anterior resection was performed, the pathological staging being pT3N0M0.
One year later, having remained free of symptoms, the patient presented with epigastric pain, nausea and vomiting. Gastroscopy revealed a third epithelial malignancy in the gastric antrum. Laparotomy showed dissemination of the cancer involving the peritoneum.
Comment
There is a relationship between the presence of chromosomal abnormalities and the tendency to develop cancer in chromosomal-instability syndromes such as Fanconi’s anaemia and ataxia-telangiectasia [1]. Chromosomal instability is also seen in other malignant disorders such as retinoblastoma, multiple endocrine neoplasia, familial colonic polyposis, malignant lesions of the cervix, Hodgkin’s disease and in patients with more than one primary neoplasm. [2] [3] [4]
The normal function of all cell-cycle control mechanisms is necessary to maintain genomic integrity. Thus, any disturbance occurring at this level will produce a disorder in DNA, with a correspondingly inadequate cell response, causing a tumour to develop.
Genetic instability and the resultant generation of tumour cell heterogeneity may be important in two areas of cancer biology. First, the generation of a cancer cell is a multi-step process, requiring the activation of dominant-acting oncogenes, inactivation of tumour suppressor genes and the acquisition of immortality. The presence of genetic instability does not necessarily mean that a cell will generate these events, but it may increase the probability. Second, an important manifestation of genetic instability and tumour cell heterogeneity is the development of variant cells within the cancer population. This results in the generation of cells that are drug-resistant, have altered antigenicity and show increased metastatic potential. Therefore, accepting chromosomal instability as a factor that increases the risk of neoplasia, such patients must be followed closely to detect recurrence or new cancers at an early stage.
Authors
- N. Carrasco, MD, Resident in Urology.
- C. Casadevall, PhD Student.
- M. Bernues, PhD Student.
- G. Nohales, MD, Resident in Urology.
- A. Gelabert-Mas, MD, PhD, Professor and Chairman.
- Correspondence: Dr N. Carrasco Canovas, Department of Urology, Hospital del Mar, Paseo Maritimo 25-29, 08003 Barcelona, Spain.
References
- ^ Heims S, Johansson B, Mertens F. Constitutional chromosome instability and cancer risk. Mut Res 1989; 221: 39-51 PubMed
- ^ Brown T, Dawson AA, McDonald IA, Bullock I, Watt JI. Chromosome damage and sister chromatid exchanges in lymphocyte cultures from patients with two primary cancers. Cancer Genet Cytogenet 1985; 17: 35-42 PubMed
- ^ Barrios L, Miro R, Caballin MR et al. Chromosome instability in bladder carcinoma patients. Cancer Genet Cytogenet 1990; 49: 107-11 PubMed
- ^ Popescu NC. Chromosome fragility and instability in human cancer. Crit Rev Oncol 1994; 5: 121-40 PubMed
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