Study on Intratumor Heterogenity of Nuclear DNA Content in Colorectal Carcinoma

The DNA content of five samples obtained from different sites in each of 67 colorectal carcinomas was measured by flow cytometry to study on intratumor heterogenity of nuclear DNA content. Among the five samples of the same tumor DNA ploidy was discordant in 16 cases and the difference in the DNA in...

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Published inNippon Daicho Komonbyo Gakkai Zasshi Vol. 45; no. 3; pp. 266 - 272
Main Authors Funabashi, K., Yanagita, K., Kuramoto, S., Andou, K., Yoshio, T., Tsujita, K., Torikoshi, Y., Yamashita, S., Kobayashi, K., Kuwabara, T., Nagasawa, Y., Hasebe, Y., Tsujimoto, S., Gotou, T., Watanabe, M.
Format Journal Article
LanguageEnglish
Published The Japan Society of Coloproctology 1992
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ISSN0047-1801
1882-9619
DOI10.3862/jcoloproctology.45.266

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Abstract The DNA content of five samples obtained from different sites in each of 67 colorectal carcinomas was measured by flow cytometry to study on intratumor heterogenity of nuclear DNA content. Among the five samples of the same tumor DNA ploidy was discordant in 16 cases and the difference in the DNA index (DI) value was found in 11 patients with aneuploidy in all specimens taken from the same tumors. Therefore intratumor DNA heterogenity was observed in twentyseven of 67 cased (40.7 %). DNA heterogenity was not associated with the location of the tumor, size, depth of tumorinvasion, lymphatic vessel invasion, lymph node metastasis, and stage. On the other hand, tumors with the presence of DNA heterogenity had significantly higher frequency of moderately differentiated adenocarcinoma, presence of venous invasion, and liver metastasis than those wdthout DNA heterogenity. The incidence of tumor with s (a2) or si (ai), liver metastasis and advanced stage more than stage III was highest in the cases with aneuploidy in all samples and the presence of intratumor DNA heterogenity. There was a good correlation between DI obtained from biopsy and resected specimen only when intratumor DNA heterogenity was not observed.
AbstractList The DNA content of five samples obtained from different sites in each of 67 colorectal carcinomas was measured by flow cytometry to study on intratumor heterogenity of nuclear DNA content. Among the five samples of the same tumor DNA ploidy was discordant in 16 cases and the difference in the DNA index (DI) value was found in 11 patients with aneuploidy in all specimens taken from the same tumors. Therefore intratumor DNA heterogenity was observed in twentyseven of 67 cased (40.7 %). DNA heterogenity was not associated with the location of the tumor, size, depth of tumorinvasion, lymphatic vessel invasion, lymph node metastasis, and stage. On the other hand, tumors with the presence of DNA heterogenity had significantly higher frequency of moderately differentiated adenocarcinoma, presence of venous invasion, and liver metastasis than those wdthout DNA heterogenity. The incidence of tumor with s (a2) or si (ai), liver metastasis and advanced stage more than stage III was highest in the cases with aneuploidy in all samples and the presence of intratumor DNA heterogenity. There was a good correlation between DI obtained from biopsy and resected specimen only when intratumor DNA heterogenity was not observed.
Author Yamashita, S.
Tsujimoto, S.
Hasebe, Y.
Funabashi, K.
Yanagita, K.
Andou, K.
Nagasawa, Y.
Tsujita, K.
Kuramoto, S.
Kobayashi, K.
Kuwabara, T.
Watanabe, M.
Torikoshi, Y.
Yoshio, T.
Gotou, T.
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References 24) Toshima K, Nagorney DM, Rainwater LM, et al : Prognostic significance of nuclear deoxyribonucleic acid ploidy patterns in rese-cted hepatic metastasis from colorectal carcinoma. Surgery 102 : 635-641, 1987
17) Hiddemann W, Von Basewitz DB, Kleinmer H, et al: DNA stemline heterogeneity in colorectal cancer. Cancer 58 : 258-263, 1986
16) Tribukait B, Hammarrberg C, Rubio C : Ploidy and proliferation patterns in colorectal adenocarcinomas related to Dukes' classification and to histopathological differentiation. Acta Pathol Microbiol Immunol Scand Sect A 91 : 89-95, 1983
11) 鈴木宏志,山村剛司,松本好市ほか:大腸癌の腫瘍細胞のDNA ploidyと術後累積生存率の関連.日本大腸肛門病会誌43:1419-1422,1990
12) Rognum TO, Thorud E, Lund E : Survival of large bowel carcinoma patients with different DNA ploidy. Br J Cancer 56 : 633-636, 1987
5) Kokal WA, Garden RL, Sheibani K, et al : Tumor DNA content in resectable primary colorectal carcinoma. Ann Surg 209 : 188-193, 1989
7) 武川啓一:直腸癌とDNA-予後因子としてのDNA量測定の意義-.日外会誌91:980-986,1990
2) 安藤善郎:DNA flowcytometryからみた大腸癌の予後4関する検討.日外会誌911700-1709,1990
4) Scott NA, Rainwater LM, Wieand HS, et al: The relative prognostic value of flow cytometric DNA analysis and conventional clinicopathologic criteria in patients with operable rectal carcinoma. Dis Colon Rectum 30 : 513-520, 1987
22) 丸岡康洋,前谷俊三,戸部隆吉:大腸癌の予後に関する病理学的因子の統計学的解析.日外会誌89:181-191,1988
10) 辻田和紀,船橋公彦,渡邊正志ほか:Fiowcy-tometryによる大腸癌核DNA量測定の意義.日消外会誌24:2176-2182,1991
8) 小坂健夫,伊井徹,松本尚ほか:FCMをもちいたDNA PIoidyおよびDNA Indexと大腸癌の予後に関する検討.日本大腸肛門病会誌43:61-66,1990
19) Scott NA, Grande JP, Weiland LH, et al : Flow cytometric DNA patterns from colorectal cancers. -How reproducible are they? Mayo Clin Proc 72: 331-337, 1987
9) Giaretti W, Danova M, GTido E, et al: Flow cytometric DNA index in the prognosis of colorectal cancer. Cancer 67 : 1921- 1927, 1991
3) 石川啓,田川泰,中越享ほか:多変量解析による大腸癌核DNA量の予後因子としての評価.日消外会誌22:1806-1860,1989
21) 飯田明:大腸癌の組織型と治療成積.とくに高分化腺癌と中分化腺癌の生存率の違いについて,目本大腸肛門病会誌43:533-541,1990
20) Wersto RP, Liblit RL, Deitch D, et al: Variability in DNA measurements in multiple tumor samples of human colonic carcinoma. Cancer 67 : 106-115, 1991
23) 山口明夫,石田哲也,西村元一ほか:核DNAよりみた大腸癌転移例(FCMを用いた検討).日外会誌91:1591-1595,1990
15) Merkel ED, Mcguire LW : Ploidy, proliferative activity and prognosis DNA flow cytometry of solid tumors. Cancer 65 : 1194- 1205, 1990
1) Wolley RC, Schreiber K, Koss LG, et al: DNA distribution in human colon carcino-mas and its relationship to clinical behavior. J Natl Cancer Inst 69 : 15-22, 1982
6) Jones DJ, Moore M, Schofield PF : Prognostic significance of DNA ploidy in colorectal cancer : A prospective flow cytometric study. Br J Surg 75 : 28-33, 1988
18) Sasaki K, Hashimoto T, Kawachino K, et al: Intratumoral regional differences in DNA ploidy of gastrointestinal carcinomas. Cancer 62 : 2569-2575, 1988
13) Heppner GH : Tumor heterogeneity. Cancer Res 44, 2259-2265, 1984
14) 大腸癌研究会編:大腸癌取扱い規約.改訂第4版.東京,金原出版,1985
References_xml – reference: 10) 辻田和紀,船橋公彦,渡邊正志ほか:Fiowcy-tometryによる大腸癌核DNA量測定の意義.日消外会誌24:2176-2182,1991
– reference: 14) 大腸癌研究会編:大腸癌取扱い規約.改訂第4版.東京,金原出版,1985
– reference: 23) 山口明夫,石田哲也,西村元一ほか:核DNAよりみた大腸癌転移例(FCMを用いた検討).日外会誌91:1591-1595,1990
– reference: 11) 鈴木宏志,山村剛司,松本好市ほか:大腸癌の腫瘍細胞のDNA ploidyと術後累積生存率の関連.日本大腸肛門病会誌43:1419-1422,1990
– reference: 15) Merkel ED, Mcguire LW : Ploidy, proliferative activity and prognosis DNA flow cytometry of solid tumors. Cancer 65 : 1194- 1205, 1990
– reference: 1) Wolley RC, Schreiber K, Koss LG, et al: DNA distribution in human colon carcino-mas and its relationship to clinical behavior. J Natl Cancer Inst 69 : 15-22, 1982
– reference: 17) Hiddemann W, Von Basewitz DB, Kleinmer H, et al: DNA stemline heterogeneity in colorectal cancer. Cancer 58 : 258-263, 1986
– reference: 20) Wersto RP, Liblit RL, Deitch D, et al: Variability in DNA measurements in multiple tumor samples of human colonic carcinoma. Cancer 67 : 106-115, 1991
– reference: 6) Jones DJ, Moore M, Schofield PF : Prognostic significance of DNA ploidy in colorectal cancer : A prospective flow cytometric study. Br J Surg 75 : 28-33, 1988
– reference: 3) 石川啓,田川泰,中越享ほか:多変量解析による大腸癌核DNA量の予後因子としての評価.日消外会誌22:1806-1860,1989
– reference: 16) Tribukait B, Hammarrberg C, Rubio C : Ploidy and proliferation patterns in colorectal adenocarcinomas related to Dukes' classification and to histopathological differentiation. Acta Pathol Microbiol Immunol Scand Sect A 91 : 89-95, 1983
– reference: 19) Scott NA, Grande JP, Weiland LH, et al : Flow cytometric DNA patterns from colorectal cancers. -How reproducible are they? Mayo Clin Proc 72: 331-337, 1987
– reference: 21) 飯田明:大腸癌の組織型と治療成積.とくに高分化腺癌と中分化腺癌の生存率の違いについて,目本大腸肛門病会誌43:533-541,1990
– reference: 9) Giaretti W, Danova M, GTido E, et al: Flow cytometric DNA index in the prognosis of colorectal cancer. Cancer 67 : 1921- 1927, 1991
– reference: 4) Scott NA, Rainwater LM, Wieand HS, et al: The relative prognostic value of flow cytometric DNA analysis and conventional clinicopathologic criteria in patients with operable rectal carcinoma. Dis Colon Rectum 30 : 513-520, 1987
– reference: 8) 小坂健夫,伊井徹,松本尚ほか:FCMをもちいたDNA PIoidyおよびDNA Indexと大腸癌の予後に関する検討.日本大腸肛門病会誌43:61-66,1990
– reference: 5) Kokal WA, Garden RL, Sheibani K, et al : Tumor DNA content in resectable primary colorectal carcinoma. Ann Surg 209 : 188-193, 1989
– reference: 24) Toshima K, Nagorney DM, Rainwater LM, et al : Prognostic significance of nuclear deoxyribonucleic acid ploidy patterns in rese-cted hepatic metastasis from colorectal carcinoma. Surgery 102 : 635-641, 1987
– reference: 13) Heppner GH : Tumor heterogeneity. Cancer Res 44, 2259-2265, 1984
– reference: 18) Sasaki K, Hashimoto T, Kawachino K, et al: Intratumoral regional differences in DNA ploidy of gastrointestinal carcinomas. Cancer 62 : 2569-2575, 1988
– reference: 7) 武川啓一:直腸癌とDNA-予後因子としてのDNA量測定の意義-.日外会誌91:980-986,1990
– reference: 22) 丸岡康洋,前谷俊三,戸部隆吉:大腸癌の予後に関する病理学的因子の統計学的解析.日外会誌89:181-191,1988
– reference: 12) Rognum TO, Thorud E, Lund E : Survival of large bowel carcinoma patients with different DNA ploidy. Br J Cancer 56 : 633-636, 1987
– reference: 2) 安藤善郎:DNA flowcytometryからみた大腸癌の予後4関する検討.日外会誌911700-1709,1990
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