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Allelic loss at TP53 in metastatic human endometrial carcinomas

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Abstract

Loss of heterozygosity (LOH) is implicated in the initiation and progression of various human neoplasia, and is observed in both early or in advanced-stage human cancers. The current study was aimed at investigating the frequency of LOH TP53 in human endometrial carcinoma (EC) metastases. LOH was analyzed using 3 intragenic polymorphisms in 38 primary ECs and corresponding metastatic lesions. Allelic loss at intron 1 was detected in 14 out of 38 (37%) primary carcinomas and in 11 out of 38 (29%) metastatic lesions. LOH at intron 1 in primary and metastatic tumors was concomitantly noted in 8 out of 38 (21%) cases. LOH at intron 4 was seen in 46% (17 out of 37) primary ECs and in 35% (13 out of 37) metastatic lesions. LOH at intron 4 in primary tumor/metastasis was concomitantly demonstrated in 27% (10 out of 33) cases. Allelic loss at exon 4 was detected in 5 out of 33 (15%) primary ECs and in one out of 33 (3%) corresponding metastases. Coexistence of LOH TP53 in primary ECs with metastases at intron 1 and intron 4 was observed in three out of 33 (9%) cases. Correlation between allelic loss at intron 1 in primary ECs and corresponding metastases was found (R = 0.475, p = 0.003). Moreover, there was correlation between LOH at intron 1 in metastastic ECs and allelic imbalance at intron 4 in primary uterine tumors (R = 0.416, p = 0.01). There was a relationship between LOH at intron 4 in primary ECs and corresponding metastatic lesions (R = 0.457, p = 0.004). LOH TP53 at intron 4 correlated with the presence of the neoplasm in the uterine cervix (R = 0.319, p = 0.049), and with the non-endometrioid type of primary tumor (R = 0.371, p = 0.024). There was a significant correlation between exon 4 LOH and patient age (less or equal to 50 years and above this age; R = −0.375, p = 0.032). p53 overexpression was present in thirteen out of 38 (34%) cases, both in primary ECs and in metastatic lesions. Overexpression of p53 was higher in non-endometrioid ECs (three out of 5; 60%) than in endometrioid-type uterine tumors (ten out of 33; 30.3%; p = 0.315). p53 overexpression correlated with the presence of cancer in the lumen of fallopian tube(s) (R = 0.032, p = 0.046), and with allelic loss at intron 1 in primary ECs (R = 0.599, p = 0.0001). In conclusion, LOH occurs not only in primary uterine tumors but also in corresponding metastases, with the higher incidence being reported at intron 4 of the TP53. A significant link existed between LOH TP53 at intron 1 and p53 overexpression in primary ECs, but not in the corresponding metastatic lesions.

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Abbreviations

LOH:

Loss of heterozygosity

EC:

Endometrial cancer

G1:

Well-differentiated cancer

G2:

Moderately-differentiated cancer

G3:

Poorly-differentiated cancer

IHC:

Immunohistochemistry

RFLP:

Restriction fragment length polymorphism

VNTR:

Variable number of tandem repeats

VSI:

Vascular space invasion

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Acknowledgments

The authors are grateful to the staff of the Department of Pathology, Medial University of Lublin, Lublin, Poland, for the pathological assessment of the material. This research was granted by Medical University of Lublin, Lublin, Poland (Dz. St. 326/07 and 326/08 to A.S.).

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Authors and Affiliations

  1. IInd Department of Gynecology, Medical University of Lublin, 8 Jaczewski street, 20-954, Lublin, Poland

    Wiktor Szewczuk, Dorota Prządka-Rabaniuk, Piotr Olcha & Andrzej Semczuk

  2. Department of Pathology, Medical University of Lublin, Lublin, Poland

    Danuta Skomra

  3. Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland

    Marek Cybulski

  4. Department of Human Genetics, Medical University of Lublin, Lublin, Poland

    Agata Filip

  5. Department of Gynecology, Bialystok Medical University, Bialystok, Poland

    Maciej Jóźwik

  6. Department of Pathology, Otto-von-Guericke University, Magdeburg, Germany

    Albert Roessner

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  1. Wiktor Szewczuk
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  2. Danuta Skomra
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Correspondence to Andrzej Semczuk.

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Szewczuk, W., Skomra, D., Cybulski, M. et al. Allelic loss at TP53 in metastatic human endometrial carcinomas. Clin Exp Metastasis 26, 789–796 (2009). https://doi.org/10.1007/s10585-009-9278-3

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  • DOI: https://doi.org/10.1007/s10585-009-9278-3

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