| Uterine leiomyoma is one of the most frequent neoplasms, occurring in 25% to 77% of adult women. While most of the cases are benign, its behavior in patients remains unpredicatable. Some histologically benign tumors may show aggressiveness or even metastasis to distant organs. These cases carry two or more nodules, falling into the category of multiple uterine leiomyomas. To disclose relationship among different tumor nodules in multiple cases may help to describe their biological behavior.Random inactivation of one X-chromosome in somatic cells offers a probability for the clonality analysis. The inactivation pattern can also be used as a parameter to describle the relationship of multiple lesions in a case. Recently, we have established a clonality assay based on X-chromosome polymorphism at the phosphoglycerate kinase (PGK) locus, our data indicating that some multiple leiomyomas may be unicentric. In this study, we established the non-isotopic clonality assay based on inactivation patterns of the polymorphic X-chromosomes at androgen receptor (AR) locus, in order to approve our previous finding. The following tests were performed: 1) Genomic DNA was extracted from fresh neoplastic tissue and the peritumorous normal smooth muscle tissue as a control in 111 cases. 2) The associations between the number of short tandem repeat (STR) CAG and the relarion between and number of tumor nodules in multiple cases are investigated. 3) Multiple leiomyomas were examined for the possible link between occurrence of the unicentric type and their mitotic figures, nuclear bizarrity, myxoid and hyaline degeneration.A total number of 111 cases of leiomyomas and one leiomyosarcoma were examined, 89% showing the length polymorphism for AR gene. Loss of X-chromosome inactivation mosiacismwas observed in all of the 265 tumor nodes examined from 64 cases, reflecting their clonal cellular composition. In a multi-nodular leiomyosarcoma, 7 apparently discrete nodules presented the same AR allele inactivation pattern. The data demonstrated the same origin of different nodules by invasion. The patient had died of metastasis for 24 months after operation. The inter-nodular relationship also was evaluated by their X-chromosome inactivation patterns in 48 cases of multiple uteine leiomyomas. The same inactivated allele was found among all nodules in 24 (50.0%), and among most of nodules in 5 (10.42%). Some of them are unicentric or mixed type, resembling representation of the multi-nodular leiomyosarcoma. Nineteen cases (39.58%) showed near to random distribution of the inactivated alleles among different nodes, indicating their multicentric origins. The type difference was found to be associated with the number of nodules, mitoactivity and myoxid degeneration, but not with occurrence of bizarre nuclei and hyaline degeneration. In addition, an identical mutation and loss of heterozygosity were found at the AR locus in two apparently discrete tumor nodules in one case. This provided further evidence for the unicellular origin of these lesions.Length polymorphism of the STR (CAG) has been associated to the prediposhion of several diseases. It is also assayed for the possible link to the multiple uterine leiomyomas. Number of the CAG repeats in a reference group ranged from 16 to 26, with their mean value being 19.6. For leiomyoma with one, two or three and more than three nodules, the mean values were 21.2, 21.3 and 21.8. The difference was statistically significant, indicating a predisposing role of the longer STR in the development of multiple uterine leiomyomas. The mean value of the CAG repeat numbers in multiple leiomyomas of the unicentric and mixed types were 20.4. being significantly smaller than that in the multicentric cases (22.1), further revealing that the unicentric and multicentric uterine leiomyomas might develop in different mechanisms.In the study, we have approved our previous finding that the multi-nodular leiomyomas may be classified into multicentric and unicentric (mulrifocal) types, as well as a...
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