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The 6p21 chromosome region is nonrandomly involved in endometrial polyps
GYNECOLOGIC
ONCOLOGY
46,
393-396 (1992)
CASE REPORT The 6~21 Chromosome Region Is Nonrandomly Involved in Endometrial Polyps PAOLA DAL GIN,* FRANK DE
WOLF,? PATRICK KLERCKX,$ AND HERMAN VAN DEN BERGHE*
*Center for Human Genetics and the TDepartment of Obstetrics and Gynecology, University He&g Hartkliniek, Asse, Belgium Received December
of Leuven; and the *Department
of Pathology,
26, 1991
visualization of the uterine cavity because of adherent clots in the right horn. Microscopic examination of the curettage products revealed fragments of a benign involuted glandular endometrial polyp. After the curettage the patient who was not given any hormonal treatment was free of symptoms for 8 months. Then she presented again with vaginal bleeding and a hysterectomy and a bilateral adnexectomy were performed. The size of the uterus was 10 x 6 x 8 cm. INTRODUCTION Opening of the uterine cavity revealed a pedunculated Endometrial polyps are benign overgrowths of endo- polyp. Samples of the polyp and of the myomata were metrial tissue, occurring mostly in women between 40 taken for cytogenetic examination. Microscopy of the resected specimen showed a glanand 50 years of age, originating anywhere in the uterine cavity and varying in size from a few milimeters to a mass dulocystic polyp (Fig. l), a glandulocystic hyperplastic filling the entire endometrial cavity. Malignant transfor- endometrium, several benign leiomyomata, and many foci mation is rare (~0.5%) and polyps have been found in of adenomyosis. The ovaries showed postmenopausal atrophy. 20% of uteri with endometrial carcinoma [I]. Few endometrial polyps have been cytogenetically investigated, but the four cases reported all showed simple CYTOGENETIC STUDIES chromosome changes mainly involving 6p. Short-term cultures of a tumor sample from the uterine leiomyoma and from the endometrial polyp were perCASE REPORT formed according to the procedures previously described The patient went into menopause at the age of 50. She [2,3]. Briefly, after overnight collagenase disaggregation, has three children, had no abortions, and has a blank the cells, from both samples, were resuspended in commedical history. Shortly after menopause she complained plete RPM1 medium, plated in chambers, and incubated heavily of hot flushes. Treatment with conjugated estro- in 5% CO2 atmosphere at 37°C. The chambers were harvested after 5 days following an in situ harvesting progenes at a daily dose of 0.625 mg was prescribed. After 4 months of treatment she presented at the out- cedure, including overnight exposure to Colcemid, hypatient clinic with irregular vaginal bleedings. Clinical and potonic treatment (0.8% sodium citrate) for 30 min at echographic gynecological examination revealed a poly- 37”C, and at least three fixations in 3 : 1 methanol : acetic fibromatous uterus and normal adnexae. The estrogen acid fixative (v/v). Slides were air-dried using airflow from treatment was stopped and a hysteroscopy and curettage an aquarium pump and G-banded [4]. were performed. At hysteroscopy there was no complete Fourteen out of 15 metaphases obtained from the enAn inverted chromosome 6, at bands p21 and q22, has been found as the sole chromosome abnormality in an endometrial polyp from a SO-year-old woman. Since two out of three previously reported endometrial polyps showed a rearrangement of the same band 6~21, the nonrandom involvement of the terminal region of the short arm of chromsome 6 in this benign tumor can be supported. 0 1992 Academic Press, Inc.
393 0090-8258@2$4.00 Copyright 0 1992 by Academic Press, Inc. All rights of reproduction in any form reserved.
FIG. 1. (a) Overview of a glandular endometrial polyp overlying an atrophic endometrium. Note the presence of a cystic dilated gland. H&E stained paraffin section. (b) Detail from the endometrial polyp shown in a. In the stromal component of the polyp, several clusters of small vessels with a rather thick vessel wall can be recognized. H&E stained paraffin section. 394
395
CASE REPORT
FIG. 2. G-Banded karyotype showing inv(6)(p21q22) as the only chromosome abnormality in an endometrial polyp. Inset: Partial karyotypes from two other metaphases.
dometrial polyp culture, showed an inversion of 1 chromosome 6 at bands p21 and q22, inv (6)(p21q22), as the only chromosome abnormality (Fig. 2). The remaining cell presented a normal karyotype as well as the 20 metaphases analyzed from the uterine leiomyoma culture. DISCUSSION Recently, the presence of chromosome abnormalities in benign tumors has been widely reported and specific chromosome regions have been found to be important in benign proliferations [5]. The terminal region of the short arm of chromosome 6, 6p21+6p23, was found to be involved in lipomas, uterine leiomyomas, and pleomorphic adenomas of the salivary gland, as a primary change as well as a secondary change. A t(6;20)(p21;q13) has already been reported by our group, in two distinct endometrial polyps [6,7] (Table 1). Here we describe another example of 6p involvement, inv(6)(p21q22), in an endometrial polyp, indicating that this region of 6p is frequently rearranged in this type of tumor.
The importance of the finding of a consistently occurring chromosome change in a tumor is that it indicates where to look for the molecular change(s) underlying the pathogenesis of the tumor. From what is already known from other model systems in leukemia or in solid tumors, inversions as well as translocations may impair the functioning of a so-called recessive suppressor gene, or, more likely, disrupt the control system of a dominant oncogene or give rise to a new hybrid sequence with oncogenic potential.
TABLE Cytogenetic
1
Investigationsin Endometrial Polyps
(1) 46,XX,inv(l2)(pll,2q13) (2) 46,XX,t(6;20)(p21;q13),der(8q) (3) 46,XX,t(6;20)@21;q13),(ins(16;1) (@%l32q42) (4) 46,XX,inv(6)@21q22)
Walter et al., 1989 [8] Dal Cin et al., 1991 [6] Speleman et al., 1991 [7] Present case
DAL CIN ET AL.
396
ACKNOWLEDGMENTS Supported by the Inter-University Network for Fundamental research 3. sponsored by the Belgian Government (1991-1995) and Grant 3.007490 of the FGWO, Belgium. The authors thank Magda Dahaen and Lutgarde Meekers for technical assistance and Rita Logist for clerical 4. assistance Note added in
proof. After this manuscript was accepted we found
another endometrial polyp with a dup(6)(p21.lp21.3) abnormality.
as the sole 6.
7.
REFERENCES 1. Kurman, R. J., and Mzur, M. T. Benign diseases of trium, in Blaustein’s pathology of the female genital Kurman, Ed.), Springer-Verlag, New York, 3rd ed., (1987). 2. Peakman, D. C., Moreton, M. F., and Robinson, A.
5.
the endometract, (R. J. pp. 305-307 Prenatal di-
8.
agnosis: Techniques used to help in ruling out maternal contamination, 1. Med. Genet. 14, 37-39 (1977). Limon, J., Dal Cin, P., and Sandberg, A. A. Application of longterm collagenase disaggregation for the cytogenetic analysis of human solid tumors, Cancer Gener. Cyrogener. 23, 305-313 (1986). de la Maza, L. M., and Sanchez, 0. Simultaneous G and C banding of human chromosomes, J. Med. Gener. 13, 235-236 (1976). Sreekantaiah, C., and Sandberg, A. A. Clustering of aberrations to specific chromosome regions in benign neoplasms, Inr. J. Cancer 48, 194-198 (1991). Dal Cin, P., Brosens, I., and Van Den Berghe, H. Involvement of 6p in an endometrial polyp, Cancer Gener. Cytogener. 51, 279-280 (1991). Speleman, F., Dal Cin, P., Van Roy, N., Van Marck, E., Buytaert, P., Van Den Berghe, H., and Leroy, J. G. Is t(6;2O)(p21;q13) a characteristic chromosome change in endometrial polyps? Genes, Chromosomes Cancer 3, 318-319 (1991). Walter, T. A., Fan, S. X., MedchiII, M. T., Berger, C. S., Decker, H. J. H., and Sandberg, A. A. Inv(12)(p11.2q13) in an endometrial polyp, Cancer Gener. Cyrogenet. 41, 99-100 (1989).
ONCOLOGY
46,
393-396 (1992)
CASE REPORT The 6~21 Chromosome Region Is Nonrandomly Involved in Endometrial Polyps PAOLA DAL GIN,* FRANK DE
WOLF,? PATRICK KLERCKX,$ AND HERMAN VAN DEN BERGHE*
*Center for Human Genetics and the TDepartment of Obstetrics and Gynecology, University He&g Hartkliniek, Asse, Belgium Received December
of Leuven; and the *Department
of Pathology,
26, 1991
visualization of the uterine cavity because of adherent clots in the right horn. Microscopic examination of the curettage products revealed fragments of a benign involuted glandular endometrial polyp. After the curettage the patient who was not given any hormonal treatment was free of symptoms for 8 months. Then she presented again with vaginal bleeding and a hysterectomy and a bilateral adnexectomy were performed. The size of the uterus was 10 x 6 x 8 cm. INTRODUCTION Opening of the uterine cavity revealed a pedunculated Endometrial polyps are benign overgrowths of endo- polyp. Samples of the polyp and of the myomata were metrial tissue, occurring mostly in women between 40 taken for cytogenetic examination. Microscopy of the resected specimen showed a glanand 50 years of age, originating anywhere in the uterine cavity and varying in size from a few milimeters to a mass dulocystic polyp (Fig. l), a glandulocystic hyperplastic filling the entire endometrial cavity. Malignant transfor- endometrium, several benign leiomyomata, and many foci mation is rare (~0.5%) and polyps have been found in of adenomyosis. The ovaries showed postmenopausal atrophy. 20% of uteri with endometrial carcinoma [I]. Few endometrial polyps have been cytogenetically investigated, but the four cases reported all showed simple CYTOGENETIC STUDIES chromosome changes mainly involving 6p. Short-term cultures of a tumor sample from the uterine leiomyoma and from the endometrial polyp were perCASE REPORT formed according to the procedures previously described The patient went into menopause at the age of 50. She [2,3]. Briefly, after overnight collagenase disaggregation, has three children, had no abortions, and has a blank the cells, from both samples, were resuspended in commedical history. Shortly after menopause she complained plete RPM1 medium, plated in chambers, and incubated heavily of hot flushes. Treatment with conjugated estro- in 5% CO2 atmosphere at 37°C. The chambers were harvested after 5 days following an in situ harvesting progenes at a daily dose of 0.625 mg was prescribed. After 4 months of treatment she presented at the out- cedure, including overnight exposure to Colcemid, hypatient clinic with irregular vaginal bleedings. Clinical and potonic treatment (0.8% sodium citrate) for 30 min at echographic gynecological examination revealed a poly- 37”C, and at least three fixations in 3 : 1 methanol : acetic fibromatous uterus and normal adnexae. The estrogen acid fixative (v/v). Slides were air-dried using airflow from treatment was stopped and a hysteroscopy and curettage an aquarium pump and G-banded [4]. were performed. At hysteroscopy there was no complete Fourteen out of 15 metaphases obtained from the enAn inverted chromosome 6, at bands p21 and q22, has been found as the sole chromosome abnormality in an endometrial polyp from a SO-year-old woman. Since two out of three previously reported endometrial polyps showed a rearrangement of the same band 6~21, the nonrandom involvement of the terminal region of the short arm of chromsome 6 in this benign tumor can be supported. 0 1992 Academic Press, Inc.
393 0090-8258@2$4.00 Copyright 0 1992 by Academic Press, Inc. All rights of reproduction in any form reserved.
FIG. 1. (a) Overview of a glandular endometrial polyp overlying an atrophic endometrium. Note the presence of a cystic dilated gland. H&E stained paraffin section. (b) Detail from the endometrial polyp shown in a. In the stromal component of the polyp, several clusters of small vessels with a rather thick vessel wall can be recognized. H&E stained paraffin section. 394
395
CASE REPORT
FIG. 2. G-Banded karyotype showing inv(6)(p21q22) as the only chromosome abnormality in an endometrial polyp. Inset: Partial karyotypes from two other metaphases.
dometrial polyp culture, showed an inversion of 1 chromosome 6 at bands p21 and q22, inv (6)(p21q22), as the only chromosome abnormality (Fig. 2). The remaining cell presented a normal karyotype as well as the 20 metaphases analyzed from the uterine leiomyoma culture. DISCUSSION Recently, the presence of chromosome abnormalities in benign tumors has been widely reported and specific chromosome regions have been found to be important in benign proliferations [5]. The terminal region of the short arm of chromosome 6, 6p21+6p23, was found to be involved in lipomas, uterine leiomyomas, and pleomorphic adenomas of the salivary gland, as a primary change as well as a secondary change. A t(6;20)(p21;q13) has already been reported by our group, in two distinct endometrial polyps [6,7] (Table 1). Here we describe another example of 6p involvement, inv(6)(p21q22), in an endometrial polyp, indicating that this region of 6p is frequently rearranged in this type of tumor.
The importance of the finding of a consistently occurring chromosome change in a tumor is that it indicates where to look for the molecular change(s) underlying the pathogenesis of the tumor. From what is already known from other model systems in leukemia or in solid tumors, inversions as well as translocations may impair the functioning of a so-called recessive suppressor gene, or, more likely, disrupt the control system of a dominant oncogene or give rise to a new hybrid sequence with oncogenic potential.
TABLE Cytogenetic
1
Investigationsin Endometrial Polyps
(1) 46,XX,inv(l2)(pll,2q13) (2) 46,XX,t(6;20)(p21;q13),der(8q) (3) 46,XX,t(6;20)@21;q13),(ins(16;1) (@%l32q42) (4) 46,XX,inv(6)@21q22)
Walter et al., 1989 [8] Dal Cin et al., 1991 [6] Speleman et al., 1991 [7] Present case
DAL CIN ET AL.
396
ACKNOWLEDGMENTS Supported by the Inter-University Network for Fundamental research 3. sponsored by the Belgian Government (1991-1995) and Grant 3.007490 of the FGWO, Belgium. The authors thank Magda Dahaen and Lutgarde Meekers for technical assistance and Rita Logist for clerical 4. assistance Note added in
proof. After this manuscript was accepted we found
another endometrial polyp with a dup(6)(p21.lp21.3) abnormality.
as the sole 6.
7.
REFERENCES 1. Kurman, R. J., and Mzur, M. T. Benign diseases of trium, in Blaustein’s pathology of the female genital Kurman, Ed.), Springer-Verlag, New York, 3rd ed., (1987). 2. Peakman, D. C., Moreton, M. F., and Robinson, A.
5.
the endometract, (R. J. pp. 305-307 Prenatal di-
8.
agnosis: Techniques used to help in ruling out maternal contamination, 1. Med. Genet. 14, 37-39 (1977). Limon, J., Dal Cin, P., and Sandberg, A. A. Application of longterm collagenase disaggregation for the cytogenetic analysis of human solid tumors, Cancer Gener. Cyrogener. 23, 305-313 (1986). de la Maza, L. M., and Sanchez, 0. Simultaneous G and C banding of human chromosomes, J. Med. Gener. 13, 235-236 (1976). Sreekantaiah, C., and Sandberg, A. A. Clustering of aberrations to specific chromosome regions in benign neoplasms, Inr. J. Cancer 48, 194-198 (1991). Dal Cin, P., Brosens, I., and Van Den Berghe, H. Involvement of 6p in an endometrial polyp, Cancer Gener. Cytogener. 51, 279-280 (1991). Speleman, F., Dal Cin, P., Van Roy, N., Van Marck, E., Buytaert, P., Van Den Berghe, H., and Leroy, J. G. Is t(6;2O)(p21;q13) a characteristic chromosome change in endometrial polyps? Genes, Chromosomes Cancer 3, 318-319 (1991). Walter, T. A., Fan, S. X., MedchiII, M. T., Berger, C. S., Decker, H. J. H., and Sandberg, A. A. Inv(12)(p11.2q13) in an endometrial polyp, Cancer Gener. Cyrogenet. 41, 99-100 (1989).