IOTH ANNIVERSARY ARTICLE Chromosomal Patterns in Human Benign Uterine Leiomyomas Joachim Mark, Guillaume Havel, Cecilia Grepp, Rigmor Dahlenfors, and Barbro Wedell
ABSTRACT: Chromosomal observations by banding technique in 18 short-term cultured human uterine leiomyomas are reported. Half of the tumors had a primary or secondary abnormal stemline. They were usually characterized only by structural changes, in particular reciprocal translocations or insertions. Reviewing already published cases together with the new material confirmed that the aberrations in abnormal stemlines predominantly affected chromosomes 1, 2, 6, 7, 12, 14, and X. In these chromosomes the regions lp36, 2p24, 6p12-21, 7q21-31, 12q13-15, 14q22-24, and the short arm of the X chromosome were preferentially affected. As in two other thoroughly studied human benign tumors, the pleomorphic adenoma and the meningioma, the very specific but sometimes complex chromosomal aberrations in leiomyomas could well be events of primary evolutionary importance. Likewise, in cases with a normal stemline, it is possible that comparable changes in the corresponding specific chromosomal regions have occurred at a submicroscopic level. Ascertaining this possibility, as well as the role of the aberrations with regard to the benign nature of the tumors, must be the focus of future analysis using molecular techniques. INTRODUCTION We have recently reported the detailed chromosomal observations by b a n d i n g techniques in a total of 25 short-term cultured h u m a n uterine leiomyomas [1-3]. As m a n y as 15 of these m y o m a s had an abnormal primary or secondary stemline. The literature contains cytogenetic information from 65 similar short-term cultured m y o m a s [4-10]. Of these, however, only 18 had abnormal stemlines. As in another thoroughly s t u d i e d benign h u m a n tumor type, the p l e o m o r p h i c adenoma, the abnormal stemlines in leiomyomas were almost exclusively characterized by structural aberrations, in particular translocations and insertions. These abnormalities preferentially affected at least chromosomes 1, 2, 6, 12, 14, and the X chromosome, and several aberrations seemed to constitute recurrent, specific deviations. We here report the chromosomal findings in 18 new leiomyomas collected from ten different patients. Aims of the present study were 1) to further delineate the specificity of the deviations characterizing abnormal stemlines, 2) to present an appraisal of the evolutionary, and possibly primary, role of the deviations observed, 3) to evaluate the implications of the variant cells frequently found in cases with a normal stemline, and 4) to search for correlations between clinicopathologic parameFrom the Department of Cytogenetics,Central Hospital, Sk6vde, Sweden. Address reprint requests to: Dr. Joachim Mark, Department of Pathology, Central Hospital, 541 85 SkOvde, Sweden. Received April 24, 1989; accepted May 31, 1989.
© 1990 Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York, NY 10010
Cancer Genet Cytogenet44:1-13 (1990) 0165-4608/90/$03.50
2
J. Mark e! al.
Table 1
Clinicopathologic characteristics of the material and designations of the leiomyomas in Tables 2 and 3
Case no.
Age at operation ( y r )
No. of leiomyomas studied
Greatest diameter of each leiomyoma (cm)
Designation of each [eiomyoma in Tables 2 and 3
17 18 19 20 21 22 23 24 25 26
46 44 43 53 48 49 50 48 44 48
3 3 2 1 2 2 2 1 1 1
6.0/4.0/1.5 4.0/2.0/1.0 2.5/3.5 2.O 2.5/3.5 2.0/1.0 1.0/6.0 9.O 4.5 4.0
L27/L37/L38 L28/L32/L31
L29/L30 L33 L34/L41 L35/L36 L39/L40 L42 L43 L44
ters, such as age of the patient and size and histologic picture of the myoma, and cytogenetic observations.
MATERIALS AND METHODS Cultures were established from a total of 21 leiomyomas from ten patients. In each of three cases (cases 20, 21, and 26) the explanted material from one or two myomas failed to grow. The clinicopathologic data for the remaining, successfully cultured, 18 myomas are summarized in Table 1. The designations in c o l u m n s 1 and 5 of this table are a c o n t i n u a t i o n of the notation used in previous reports [1-3]. All myomas were well demarcated r o u n d or ovoid tumors. Histologically, they all showed the usual benign picture. The methods for tissue culture, chromosome preparation, and G and C b a n d i n g have been described earlier [1]. As seen in Tables 2 and 3, all myomas except for L27 and L35 were studied in two or three preparations. The observations in different preparations from a certain myoma were c o m b i n e d in Tables 2 and 3. The n o m e n c l a t u r e follows that of the ISCN [11] with one exception: S(S1,S . . . . ) is used as a symbol for the stemline.
RESULTS Myomas with a Normal Stemline Table 2 shows the chromosome counts and distribution of cells karyotyped in the n i n e myomas with a normal S (L27-L35). Three cases contained several metaphases with chromosomes long enough to allow high-resolution b a n d i n g analysis. None of these cells, however, showed any deviation from the normal. In all myomas with a normal S, there were two or more variant cells. They showed mostly n u m e r i c a l deviations, in particular, losses. However, no preferential pattern could be discerned for these abnormalities. Two myomas, L32 and L34, contained variant cells with structural deviations (Fig. 1). These anomalies were u n i q u e except far the del(10)(p11) found in two different cells in L34. Chromosome breaks were rare in myomas with a normal as well as an abnormal S. With regard to the observations to be described below, however, it is of interest to note that two cells, related to the normal S in L40, showed breaks affecting the long arm of chromosomes 7 and 12, respectively (Fig. 1).
2 1
L34 L35
1(1) 1(1) 2(2) 1(1) 2(2) -2/2
--
4(4)
22 6/8 9/14 6/7 8/12/12 8/8 8/8
7/7
7
ABSTRACT: Chromosomal observations by banding technique in 18 short-term cultured human uterine leiomyomas are reported. Half of the tumors had a primary or secondary abnormal stemline. They were usually characterized only by structural changes, in particular reciprocal translocations or insertions. Reviewing already published cases together with the new material confirmed that the aberrations in abnormal stemlines predominantly affected chromosomes 1, 2, 6, 7, 12, 14, and X. In these chromosomes the regions lp36, 2p24, 6p12-21, 7q21-31, 12q13-15, 14q22-24, and the short arm of the X chromosome were preferentially affected. As in two other thoroughly studied human benign tumors, the pleomorphic adenoma and the meningioma, the very specific but sometimes complex chromosomal aberrations in leiomyomas could well be events of primary evolutionary importance. Likewise, in cases with a normal stemline, it is possible that comparable changes in the corresponding specific chromosomal regions have occurred at a submicroscopic level. Ascertaining this possibility, as well as the role of the aberrations with regard to the benign nature of the tumors, must be the focus of future analysis using molecular techniques. INTRODUCTION We have recently reported the detailed chromosomal observations by b a n d i n g techniques in a total of 25 short-term cultured h u m a n uterine leiomyomas [1-3]. As m a n y as 15 of these m y o m a s had an abnormal primary or secondary stemline. The literature contains cytogenetic information from 65 similar short-term cultured m y o m a s [4-10]. Of these, however, only 18 had abnormal stemlines. As in another thoroughly s t u d i e d benign h u m a n tumor type, the p l e o m o r p h i c adenoma, the abnormal stemlines in leiomyomas were almost exclusively characterized by structural aberrations, in particular translocations and insertions. These abnormalities preferentially affected at least chromosomes 1, 2, 6, 12, 14, and the X chromosome, and several aberrations seemed to constitute recurrent, specific deviations. We here report the chromosomal findings in 18 new leiomyomas collected from ten different patients. Aims of the present study were 1) to further delineate the specificity of the deviations characterizing abnormal stemlines, 2) to present an appraisal of the evolutionary, and possibly primary, role of the deviations observed, 3) to evaluate the implications of the variant cells frequently found in cases with a normal stemline, and 4) to search for correlations between clinicopathologic parameFrom the Department of Cytogenetics,Central Hospital, Sk6vde, Sweden. Address reprint requests to: Dr. Joachim Mark, Department of Pathology, Central Hospital, 541 85 SkOvde, Sweden. Received April 24, 1989; accepted May 31, 1989.
© 1990 Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York, NY 10010
Cancer Genet Cytogenet44:1-13 (1990) 0165-4608/90/$03.50
2
J. Mark e! al.
Table 1
Clinicopathologic characteristics of the material and designations of the leiomyomas in Tables 2 and 3
Case no.
Age at operation ( y r )
No. of leiomyomas studied
Greatest diameter of each leiomyoma (cm)
Designation of each [eiomyoma in Tables 2 and 3
17 18 19 20 21 22 23 24 25 26
46 44 43 53 48 49 50 48 44 48
3 3 2 1 2 2 2 1 1 1
6.0/4.0/1.5 4.0/2.0/1.0 2.5/3.5 2.O 2.5/3.5 2.0/1.0 1.0/6.0 9.O 4.5 4.0
L27/L37/L38 L28/L32/L31
L29/L30 L33 L34/L41 L35/L36 L39/L40 L42 L43 L44
ters, such as age of the patient and size and histologic picture of the myoma, and cytogenetic observations.
MATERIALS AND METHODS Cultures were established from a total of 21 leiomyomas from ten patients. In each of three cases (cases 20, 21, and 26) the explanted material from one or two myomas failed to grow. The clinicopathologic data for the remaining, successfully cultured, 18 myomas are summarized in Table 1. The designations in c o l u m n s 1 and 5 of this table are a c o n t i n u a t i o n of the notation used in previous reports [1-3]. All myomas were well demarcated r o u n d or ovoid tumors. Histologically, they all showed the usual benign picture. The methods for tissue culture, chromosome preparation, and G and C b a n d i n g have been described earlier [1]. As seen in Tables 2 and 3, all myomas except for L27 and L35 were studied in two or three preparations. The observations in different preparations from a certain myoma were c o m b i n e d in Tables 2 and 3. The n o m e n c l a t u r e follows that of the ISCN [11] with one exception: S(S1,S . . . . ) is used as a symbol for the stemline.
RESULTS Myomas with a Normal Stemline Table 2 shows the chromosome counts and distribution of cells karyotyped in the n i n e myomas with a normal S (L27-L35). Three cases contained several metaphases with chromosomes long enough to allow high-resolution b a n d i n g analysis. None of these cells, however, showed any deviation from the normal. In all myomas with a normal S, there were two or more variant cells. They showed mostly n u m e r i c a l deviations, in particular, losses. However, no preferential pattern could be discerned for these abnormalities. Two myomas, L32 and L34, contained variant cells with structural deviations (Fig. 1). These anomalies were u n i q u e except far the del(10)(p11) found in two different cells in L34. Chromosome breaks were rare in myomas with a normal as well as an abnormal S. With regard to the observations to be described below, however, it is of interest to note that two cells, related to the normal S in L40, showed breaks affecting the long arm of chromosomes 7 and 12, respectively (Fig. 1).
2 1
L34 L35
1(1) 1(1) 2(2) 1(1) 2(2) -2/2
--
4(4)
22 6/8 9/14 6/7 8/12/12 8/8 8/8
7/7
7
