Cytogenetic study of 11 gastric adenocarcinomas

ELSEVIER

Cytogenetic Study of 11 Gastric Adenocarcinomas Anna D. Panani, Angeliki Ferti, S. Malliaros, and S. Raptis

ABSTRACT: We describe the cytogenetic findings in 11 gastric c a n c e r cases. Nine cases showed a variable n u m b e r of numerical and structural aberrations, while two cases had a n o r m a l karyotype. The chromosomes most f r e q u e n t l y involved are chromosome 3 in six cases, 6 in four cases, and 13 in three cases. They m a i n l y exhibited structural aberrations. A n additional segment on c h r o m o s o m e 3p was observed in three cases, while two cases had a del(3q). A der(5) c h r o m o s o m e resulting from a translocation between chromosomes 3 and 5 was observed in two cases. Both cases had also a del(6q), a der(12), a n d an add(17p) c h r o m o s o m e as c o m m o n abnormalities. Deletion of 6q chromosome distal to band 6q21 was observed in three cases. Trisomy 8 as a sole a n o m a l y was found in one case. Our cytogenetic findings are discussed in relation to the reported in the literature data.

INTRODUCTION

RESULTS

There are only a few cytogenetic studies in gastric cancer a n d so far no consistent specific c h r o m o s o m a l abnormalities have b e e n d e s c r i b e d [1-10]. In some of the cases studied simple chromosomal changes were observed, while in others very c o m p l i c a t e d abnormalities were found. A m o n g s i m p l e a b n o r m a l i t i e s an extra X chromosome, trisomy 8, 9, and 19, del(7q), a n d i(8q) have b e e n d e s c r i b e d [1, 3, 6, 7]. In cases w i t h complex karyotypes a preferential involvement of chrom o s o m e s 1, 3, 6, 7, 11, a n d 13 was observed [2, 4, 6, 8, 9]. Aberrations of c h r o m o s o m e 11p13-p15 were found by Rodriguez et al. [4] in gastric cancer cases w i t h complex karyotypes a n d it was suggested that this cytogenetic abnorm a l i t y was p r o b a b l y specific. We describe here the cytogenetic findings in 11 cases of gastric cancer.

Clinical a n d histopathologic findings, as well as the number of metaphases studied, the chromosome number, and the karyotypic abnormalities of the cases studied, are shown in Table 1. In some of the cases s t u d i e d the quality of the metaphases d i d not p e r m i t exact identification of every c h r o m o s o m e change. As is indicated in Table 1, there was frequent involvement of c h r o m o s o m e s 3 (in six cases], 6 (in four cases], a n d 13 (in three cases). Chromosomes 1, 2, 5, 12, 14, 17, a n d 20 were involved in two cases each. Chromosome 3 participated in structural changes as add(3p) and del(3q). A marker c h r o m o s o m e recognized as der[5)t(3;5) (q22-23;q32] was observed in two cases [numbers 2 and 5). Chromosome 6 participated in structural abnormalities as an del(6q), add(6q), and add(6p) chromosome. Chromosome 13 exhibited n u m e r i c a l a n d structural changes. Trisomy 8 was found as a sole a n o m a l y in one case [number 8), w h i l e in another case [number 2), there was a marker chromosome p o s s i b l y coming from an interstitial d e l e t i o n of the 8q chromosome. It is noteworthy that in case 2 all the metaphases karyotyped exhibited exactly the same abnormalities, as is shown in Table 1 a n d Figure 1. Chromosomes 1, 2, and 14 participated in n u m e r i c a l and structural rearrangements, w h i l e a der(12) and an add(17p] c h r o m o s o m e were observed in two cases each (numbers 2 and 5]. Finally, two of the cases studied h a d a n o r m a l karyotype.

MATERIALS AND METHODS Cytogenetic analysis was p e r f o r m e d on eight p r i m a r y gastric tumors a n d three metastatic ascitic effusions, by a direct m e t h o d a n d a G-banding staining technique, as has been described elsewhere [11]. None of the patients had received any preoperative chemotherapy or radiotherapy. Karyotypes were d e s c r i b e d according to the International System for H u m a n Cytogenetic Nomenclature (ISCN) [12]. Clonality was defined by the detection of two cells w i t h gain of a given chromosome or the same structural abnormality, or three cells w i t h loss of a given chromosome.

DISCUSSION

From the Second Department of lnternal Medicine, Propaedeutic of Athens University, Evangelismos Hospital, Athens, Greece. Address reprint requests to: Anna D. Panani, Second Department of Internal Medicine, Pmpaedeutic of Athens University, Evangelismos Hospital, Athens 106 76, Greece. Received April 12, 1994; accepted October 25, 1994. Cancer Genet Cytogenet 81:169-172 (1995) © Elsevier Science Inc., 1995 655 Avenue of the Americas, New York, NY 10010

Data concerning the c h r o m o s o m a l changes in gastric cancer are limited. The most frequent aberrations reported by Ochi et al. [1, 2] in six cases s t u d i e d were trisomy 12, loss of the Y chromosome, a n d structural abnormalities of chrom o s o m e s 1, 3, a n d 19. I n o n e case, an extra X c h r o m o s o m e was found a n d it was c o n s i d e r e d an initial c h r o m o s o m e change. We have previously reported six cases of gastric can-

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A . D . P a n a n i et al.

Table 1

C l i n i c a l , h i s t o p a t h o l o g i c , a n d c y t o g e n e t i c f i n d i n g s in 11 p a t i e n t s w i t h gastric c a n c e r

Histopathologic Case Age/sex data 1

73/F

2Q

64/F

3

71/F

4

72/M

5

64/F

6

67/M

7

69/M

8

68/F

9

67/F

10

31/M

11

78/M

Survival after Present diagnosis clinical (months) status

Adenocarcinoma, intestinal type, poorly differentiated Adenocarcinoma, intestinal type, poorly differentiated

43 +

Adenocarcinoma, intestinal type, moderately differentiated Adenocarcinoma, intestinal type, poorly to moderately differentiated Adenocarcinoma, intestinal type, poorly differentiated Adenocarcinoma, intestinal type, moderately to poorly differentiated Adenocarcinoma, intestinal type, moderately to poorly differentiated Adenocarcinoma, intestinal type, poorly differentiated Adenocarcinoma, poorly differentiated Adenocarcinoma intestinal type Adenocarcinoma, intestinal type, moderately differentiated

35 +

Cytogenetic findings Source of sample

Number of Chromosome metaphases number

Karyotype abnormalities

No evidence Primary of disease tumor

15

43-45

add(a)(p26), + 2mar

Dead

30

67-68

No evidence Primary of disease tumor

10

58-102

- X, - 2,t(3;5)(q22-23;q32), - 4, der(4)t(4;21) (q34;q11),der(5) t(3;5)(q22-23;q32),del(6)(q22), add(6p),der{12)add{12)(p12} del(12)(q24), - 13, - 14, + 16, add(17)(p13), - 18, + 20, - 21, + 3mar del(3)(q11),add(10)(q26),i(13) (q10),add(13)(p10), + 7mar

0

Dead

Ascitic effusion

10

45-46

46,XY

4

Dead

Primary tumor

8

47-50

der(5)t(3;5)(q22-23;q32),del(6) (q21),der(12)add(12)(p12) del(12)(q24),add(17)(p13}

21

Dead

Primary tumor

10

45-52

+ 1,add(3)(p26), + 2mar

7

Dead

Primary tumor

10

64-68

der(2;13)(q10;q10),del(6)(q22), + 2mar

7

Dead

Primary tumor

8

45-48

+8

1

Dead

Ascitic effusion

10

45-46

46,XX

10

45-46

del(1}(p31), - 20

8

62-76

add(3)(p26),add(6)(q27), add(14){q31), + 3mar

19

4+ 4+

Ascitic effusion

No evidence Primary of disease tumor No evidence Primary of disease tumor

a Numerical changes are in deviation from the triploid chromosome number.

car [3, 7] cytogenetically studied. C h r o m o s o m e s 8 a n d 9 w e r e i n v o l v e d in f o u r cases each. Xiao et al. [6] d e s c r i b e d chrom o s o m a l analysis in e i g h t p r i m a r y gastric cancers. T h r e e of t h e m h a d s i m p l e c h r o m o s o m a l c h a n g e s , i n c l u d i n g an extra X c h r o m o s o m e , del(7q), a n d t r i s o m y 8 a n d 19. T h e five o t h e r cases h a d c o m p l i c a t e d c h r o m o s o m a l c h a n g e s a n d in four of t h e m 3p - a n d 7 q - c h r o m o s o m e s w e r e noted. S e r u c a et al.

[8] d e s c r i b e d t h e c y t o g e n e t i c f i n d i n g s in 11 gastric carcinomas. The most common findings were polysomy 2 and 20 a n d r e a r r a n g e m e n t s of c h r o m o s o m e s 1, 3, 7, a n d 13. In seven of e i g h t gastric c a n c e r cases s t u d i e d by R o d r i g u e z et al. [4] aberrations of c h r o m o s o m e 11p13-p15 w e r e o b s e r v e d and it was suggested that this cytogenetic abnormality is probably specific. In the present study we describe the cytogenetic

11 Gastric A d e n o c a r c i n o m a s

171

1 3 1

| 8¸

6

9

10

11

12

A

U 13

~ 8 21

2O

19

18

17

16

15

14

s 22

mar

der (5)

del(eq)

12

tier(12)

add{17p)

F i g u r e I A) Karyotype of a cell from case 2. Arrows indicate the abnormal chromosomes. Details are given in Table 1. B) Partial karyotype of a cell from case 5 showing der(5), del(6q), der(12), and add(17p].

findings in 11 cases of gastric cancer. The chromosomes most frequently involved were 3 (in six cases), 6 (in four cases), a n d 13 (in three cases). Chromosomes 1, 2, 5, 12, 14, 17, a n d 20 also participated in abnormalities in two cases each. Chromosome 3 was involved in structural changes. Structural rearrangements of c h r o m o s o m e 3 were described as a frequent a n o m a l y in gastric cancer [2, 4, 6, 8, 9]. In two of our cases (numbers 2 a n d 5), a der(5) c h r o m o s o m e resulting from a translocation between c h r o m o s o m e s 3 and 5 was observed. It is interesting that both the above-mentioned cases also exhibited other c o m m o n abnormalities: der(12), del(6q), a n d add(17p) chromosome. Xiao et al. [6] have p r e v i o u s l y described a case of gastric cancer w i t h a similar translocation between c h r o m o s o m e s 3 and 5, w h i c h the authors considered a constitutional one. Structural aberrations of chromosome 6 as del(6q) distal to b a n d 6q21 were present in three of our cases, w h i l e an add(6q) a n d an add(6p) c h r o m o s o m e were also observed. A b n o r m a l i t i e s of c h r o m o s o m e 6 resulting in loss of the c h r o m o s o m a l segment distal to b a n d 6q21-q22 were p r e v i o u s l y noted in gastric cancer [2, 4, 8]. In three of our cases, c h r o m o s o m e 13 exhibited m o n o s o m y

or participated in translocations. A b n o r m a l i t i e s of chromosome 13 were frequently found in gastric cancer [4, 8]. Loss of heterozygosity at loci on the 13q c h r o m o s o m e has been described in gastric cancer [13], although in our cases structural changes of c h r o m o s o m e 13 were located at the centromeric region. A n extra c h r o m o s o m e 8 was observed in one of our cases as a sole anomaly. We have previously described in gastric cancer abnormalities of c h r o m o s o m e 8 as trisomy or as i(8q) [3, 7]. Xiao et al. [6] have also described trisomy 8 in a case of gastric cancer w i t h m i n i m a l c h r o m o s o m a l changes. In a case of gastric cancer w i t h long survival, prev i o u s l y described by us [7], i(8q) resulting in trisomy 8q was the sole a n o m a l y and this a b n o r m a l i t y was c o n s i d e r e d as p o s s i b l y specific, associated w i t h a good prognosis. On the other hand, i(8q) has b e e n described in three cases of advanced gastric cancer [14] a n d it was suggested that this abnormality possibly represents a secondary change associated w i t h aggressive biologic behavior of the tumor. In the present study the patient w i t h trisomy 8 as a sole a n o m a l y survived 7 m o n t h s after the initial diagnosis. The presence of trisomy 8 as a sole a n o m a l y in one of our cases, as well as

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t h e p r e s e n c e of i(SqJ as a sole a n o m a l y in a case p r e v i o u s l y r e p o r t e d by u s [7], p r o b a b l y suggest that c h r o m o s o m e 8 has a role in gastric cancer. A l t h o u g h in gastric c a n c e r a p r e f e r e n t i a l i n v o l v e m e n t of certain c h r o m o s o m e s has b e e n described, data f r o m the present s t u d y a n d f r o m cases p r e v i o u s l y r e p o r t e d in t h e literat u r e are v e r y l i m i t e d to draw c o n c l u s i o n s a b o u t specific abnormalities. Moreover, c o r r e l a t i o n of c h r o m o s o m a l c h a n g e s w i t h t h e c l i n i c a l c o u r s e of gastric c a n c e r patients is still not possible. The technical assistance of Mrs. France Kousouri-Stamatelli is gratefully acknowledged. REFERENCES

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