THE JOURNAL
Vol. 114, August
OF UROLOGY
Copyright © 1975 by The Williams & Wilkins Co.
Printed in U.S.A.
ISOCHROMOSOME 17 IN PROSTATIC CANCER MITSUO OSHIMURA
AND
AVERY A. SANDBERG
From the Roswell Park Memorial Institute, Buffalo, New York
ABSTRACT
In a continuing search for karyotypic changes characterizing vanous human cancers we have examined in detail with Q and G banding techniques the chromosomal constitution of a metastatic cancer of the prostate. The results obtained with these techniques present not only what is to our knowledge the first description of the chromosome constitution in cancer of the prostate but also the first observation of an isochromosome 17 marker in a cancerous state other than a blood disease. Only further studies on the precise identification of individual chromosomes in other cancers will reveal the significance of this marker in human cancer.
t"
Detailed chromosome analyses of human prostatic cancer, either primary or metastatic, are putatively lacking. This fact is particularly surprising since most human cancers have been analyzed karyotypically. 1 Studies on cellular deoxyribonucleic acid content of cancer of the prostate have been published and correlated with prognosis 2 but these methodologies lack the specificity and morphologic detail of chromosome analysis, particularly regarding the possibility of a specific karyotypic change characterizing all or some cancers of the prostate. The new banding techniques for studying chromosomal substructure have not only afforded a means of reliably classifying the chromosomes of the human karyotype but also have made it possible to ascertain the genesis of abnormal (marker) chromosomes in cancerous and leukemic cells, whether these be markers of abnormal or apparently normal morphology. Thus, we herein report what is to our knowledge not only the first description of the chromosomal picture in a metastatic cancer of the prostate but also the first description of an isochromosome 17 marker in a human cancer. If there is a relationship between this marker and cancer of the prostate, it certainly deserves further cytogenetic studies of the primary cancer and its metastases. CYTOGENETIC RESULTS
Examination of the bone marrow aspiration from a 57-year-old patient with prostatic cancer with metastases clearly revealed almost exclusively cancer cells in the marrow, including many large clumps of such cells. Direct bone marrow chromosome preparations showed a mode of 70 chromosomes but with considerable scatter in counts around this mode and the presence (about 15 per Accepted for publication November 22, 1974. Supported in part by a grant (CA-14555) from the National Cancer Institute.
cent) of normal diploid metaphases with 46 chromosomes (see table). The latter were undoubtedly of normal bone marrow origin. Staining with Q and G banding techniques was used to examine in detail chromosome structures on 8 abnormal metaphases. This procedure revealed remarkable numerical and structural karyotypic changes, including the presence of 2 ring chromosomes and a missing Y chromosome in every metaphase scrutinized (part A of figure). Although we could not trace the exact genesis of all marker chromosomes we could readily identify 2 apparently identical chromosomes in all the abnormal metaphases which we deem to be isochromosomes. With Q banding every arm of these 2 markers had 1 proximal pale band and 1 distal band of medium fluorescence. 3 Thus, on the basis of Q and G banding patterns, we concluded that the 2 metacentric markers were isochromosomes of the long arm of 17 (part B of figure). Unfortunately, we could not observe the chromosomes of the primary cancerous tissue. However, based on our past experience, there are probably no major differences between the chromosomal pattern of the marrow metaphases and that of the primary tumor. COMMENT
Chromosomal changes in human cancer and leukemia have been found to be of significance in the diagnostic, prognostic and evolutionary aspects of these diseases. 1 Thus, not only have specific karyotypic abnormalities been described in such conditions, for example chronic myelocytic leukemia (the Ph '-chromosome), meningioma and lymphoma, but they also have been of value in the clinical and therapeutic appraisal of some of these neoplastic states. 1 The lack of cytogenetic data for cancer of the prostate is evident. As far as we know, this is the first detailed description of chromosomal abnormalities in cancer of the prostate and
250
OSHIMURA AND SANDBERG
Chromosome number distribution 46
68
69
70
71
4
2
3
12
3
72
Total
25
tients with a number of different malignant blood disorders, especially in a high proportion of patients with chronic myelocytic leukemia. •-s The new banding techniques have revealed the presence of a marker thought to be an isochromosome of the long arm of 17 in several cases of chronic myelocytic leukemia, 7 • 8 in a case of acute myelocytic leukemia" and in a case of acute lymphocytic leukemia (unpublished data). To our knowledge the identification of isochromosome 17 has not been reported to date in cancerous states other than in blood diseases. Further precise identification of individual chromosomes in other malignant diseases may reveal the occurrence of isochromosome 17 to be a rather frequent phenomenon in human cancer. Its occurrence in a prostatic cancer, in view of its lack of description so far in other cancers, should be followed by more detailed analysis of chromosomes in cancer of the prostate. REFERENCES
1. Sandberg, A. A. and Hossfeld, D. I(.: Chromosomal
2. 3. 4.
B
5.
I
A, Q banded metaphase with 2 isochromosomes 17 (thin arrows) and 2 ring chromosomes (thick arrows). B, characteristic Q and G banding patterns of isochromosome 17.
6.
7. 8.
it is hoped that this will encourage further cytogenetic analysis of this cancer. The loss of either chromosome 17 or 18 and the gain of a metacentric marker of the C-group size have been found in bone marrow cells from pa-
9.
abnormalities in human neoplasia. Ann. Rev. Med., 21: 379, 1970. Tavares, A. 8., Costa, J. and Costa Maia, J.: Correlation between ploidy and prognosis in prostatic carcinoma. J. Urol., 109: 676, 1973. Paris Conference: Standardization in Human Cytogenetics. The National Foundation, March of Dimes, 1972. De Grouchy, J., deNava, C., Feingold, J., Bilski-Pasquier, G. and Bousser, J .: Onze observations du'un modele precis d'evolution caryotypique au cours de la leucemie myeloide chronique. Europ. J. Cancer, 4: 481, 1968. Spiers, A. 8. and Baikie, A.G.: A special role of the group 17, 18 chromosomes in reticuloendothelial neoplasia. Brit. J. Cancer, 24: 77, 1970. Fleischmann, T., Hakansson, C. H., Levan, A. and Moller, T.: Multiple chromosome aberrations in a lymphosarcomatous tumor. Hereditas, 70: 243, 1972. Lobb, D. 8., Reeves, B. R. and Lawler, 8. D.: Identification of isochromosome 17 in myeloid leukaemia. Lancet, 1: 849, 1972. Rowley, J. D.: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature, 243: 290, 1973. Mitelman, F., Brandt, L. and Levan, G.: Identification of isochromosome 17 in acute myeloid leukaemia. Lancet, 2: 972, 1973.
Vol. 114, August
OF UROLOGY
Copyright © 1975 by The Williams & Wilkins Co.
Printed in U.S.A.
ISOCHROMOSOME 17 IN PROSTATIC CANCER MITSUO OSHIMURA
AND
AVERY A. SANDBERG
From the Roswell Park Memorial Institute, Buffalo, New York
ABSTRACT
In a continuing search for karyotypic changes characterizing vanous human cancers we have examined in detail with Q and G banding techniques the chromosomal constitution of a metastatic cancer of the prostate. The results obtained with these techniques present not only what is to our knowledge the first description of the chromosome constitution in cancer of the prostate but also the first observation of an isochromosome 17 marker in a cancerous state other than a blood disease. Only further studies on the precise identification of individual chromosomes in other cancers will reveal the significance of this marker in human cancer.
t"
Detailed chromosome analyses of human prostatic cancer, either primary or metastatic, are putatively lacking. This fact is particularly surprising since most human cancers have been analyzed karyotypically. 1 Studies on cellular deoxyribonucleic acid content of cancer of the prostate have been published and correlated with prognosis 2 but these methodologies lack the specificity and morphologic detail of chromosome analysis, particularly regarding the possibility of a specific karyotypic change characterizing all or some cancers of the prostate. The new banding techniques for studying chromosomal substructure have not only afforded a means of reliably classifying the chromosomes of the human karyotype but also have made it possible to ascertain the genesis of abnormal (marker) chromosomes in cancerous and leukemic cells, whether these be markers of abnormal or apparently normal morphology. Thus, we herein report what is to our knowledge not only the first description of the chromosomal picture in a metastatic cancer of the prostate but also the first description of an isochromosome 17 marker in a human cancer. If there is a relationship between this marker and cancer of the prostate, it certainly deserves further cytogenetic studies of the primary cancer and its metastases. CYTOGENETIC RESULTS
Examination of the bone marrow aspiration from a 57-year-old patient with prostatic cancer with metastases clearly revealed almost exclusively cancer cells in the marrow, including many large clumps of such cells. Direct bone marrow chromosome preparations showed a mode of 70 chromosomes but with considerable scatter in counts around this mode and the presence (about 15 per Accepted for publication November 22, 1974. Supported in part by a grant (CA-14555) from the National Cancer Institute.
cent) of normal diploid metaphases with 46 chromosomes (see table). The latter were undoubtedly of normal bone marrow origin. Staining with Q and G banding techniques was used to examine in detail chromosome structures on 8 abnormal metaphases. This procedure revealed remarkable numerical and structural karyotypic changes, including the presence of 2 ring chromosomes and a missing Y chromosome in every metaphase scrutinized (part A of figure). Although we could not trace the exact genesis of all marker chromosomes we could readily identify 2 apparently identical chromosomes in all the abnormal metaphases which we deem to be isochromosomes. With Q banding every arm of these 2 markers had 1 proximal pale band and 1 distal band of medium fluorescence. 3 Thus, on the basis of Q and G banding patterns, we concluded that the 2 metacentric markers were isochromosomes of the long arm of 17 (part B of figure). Unfortunately, we could not observe the chromosomes of the primary cancerous tissue. However, based on our past experience, there are probably no major differences between the chromosomal pattern of the marrow metaphases and that of the primary tumor. COMMENT
Chromosomal changes in human cancer and leukemia have been found to be of significance in the diagnostic, prognostic and evolutionary aspects of these diseases. 1 Thus, not only have specific karyotypic abnormalities been described in such conditions, for example chronic myelocytic leukemia (the Ph '-chromosome), meningioma and lymphoma, but they also have been of value in the clinical and therapeutic appraisal of some of these neoplastic states. 1 The lack of cytogenetic data for cancer of the prostate is evident. As far as we know, this is the first detailed description of chromosomal abnormalities in cancer of the prostate and
250
OSHIMURA AND SANDBERG
Chromosome number distribution 46
68
69
70
71
4
2
3
12
3
72
Total
25
tients with a number of different malignant blood disorders, especially in a high proportion of patients with chronic myelocytic leukemia. •-s The new banding techniques have revealed the presence of a marker thought to be an isochromosome of the long arm of 17 in several cases of chronic myelocytic leukemia, 7 • 8 in a case of acute myelocytic leukemia" and in a case of acute lymphocytic leukemia (unpublished data). To our knowledge the identification of isochromosome 17 has not been reported to date in cancerous states other than in blood diseases. Further precise identification of individual chromosomes in other malignant diseases may reveal the occurrence of isochromosome 17 to be a rather frequent phenomenon in human cancer. Its occurrence in a prostatic cancer, in view of its lack of description so far in other cancers, should be followed by more detailed analysis of chromosomes in cancer of the prostate. REFERENCES
1. Sandberg, A. A. and Hossfeld, D. I(.: Chromosomal
2. 3. 4.
B
5.
I
A, Q banded metaphase with 2 isochromosomes 17 (thin arrows) and 2 ring chromosomes (thick arrows). B, characteristic Q and G banding patterns of isochromosome 17.
6.
7. 8.
it is hoped that this will encourage further cytogenetic analysis of this cancer. The loss of either chromosome 17 or 18 and the gain of a metacentric marker of the C-group size have been found in bone marrow cells from pa-
9.
abnormalities in human neoplasia. Ann. Rev. Med., 21: 379, 1970. Tavares, A. 8., Costa, J. and Costa Maia, J.: Correlation between ploidy and prognosis in prostatic carcinoma. J. Urol., 109: 676, 1973. Paris Conference: Standardization in Human Cytogenetics. The National Foundation, March of Dimes, 1972. De Grouchy, J., deNava, C., Feingold, J., Bilski-Pasquier, G. and Bousser, J .: Onze observations du'un modele precis d'evolution caryotypique au cours de la leucemie myeloide chronique. Europ. J. Cancer, 4: 481, 1968. Spiers, A. 8. and Baikie, A.G.: A special role of the group 17, 18 chromosomes in reticuloendothelial neoplasia. Brit. J. Cancer, 24: 77, 1970. Fleischmann, T., Hakansson, C. H., Levan, A. and Moller, T.: Multiple chromosome aberrations in a lymphosarcomatous tumor. Hereditas, 70: 243, 1972. Lobb, D. 8., Reeves, B. R. and Lawler, 8. D.: Identification of isochromosome 17 in myeloid leukaemia. Lancet, 1: 849, 1972. Rowley, J. D.: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature, 243: 290, 1973. Mitelman, F., Brandt, L. and Levan, G.: Identification of isochromosome 17 in acute myeloid leukaemia. Lancet, 2: 972, 1973.
