Expression of chemoresistance-related proteins in α-fetoprotein- producing adenocarcinoma of the digestive organs

Shingo Kamoshida, Mai Suzuki, Yoichi Sakurai, Masahiro Ochiai, Fumikazu Kimura, Sadahito Kuwao, Kazuki Sakamoto, Yoshikazu Sugimoto, Masakazu Fukushima, Yutaka Tsutsumi

Research output: Contribution to journalArticle

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Abstract

α-fetoprotein-producing adenocarcinoma of the digestive organs (APAD) is known to show a poor prognosis. To clarify the characteristics of chemoresistance in APAD, three proteins of fluoropyrimidine chemotherapy association [dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and thymidylate synthase (TS)] and one protein of cisplatin association [metallothionein (MT)] were immuno-histochemically evaluated. Tissue samples were taken from 12 AFP-positive gastric cancers and 94 AFP-negative gastric cancers. Four AFP-positive cancer xenografts (one colonic, two pancreatic, and one biliary tract) and 17 AFP-negative cancer xenografts were also examined. In gastric cancers, high expression of TP was observed in 30% of AFP-negative tumors but in none of AFP-positive tumors (p=0.03). High expression of MT was found in 30% of AFP-negative tumors but in only one of the AFP-positive tumors. The TP-low and MT-low phenotype was noted in 92% of AFP-positive tumors and in 46% of AFP-negative tumors (p=0.004). None of the AFP-positive cancer xenografts revealed high TP expression and only one showed high MT expression. In the cellular level, TP and MT were scarcely co-expressed with AFP in either gastric cancer or xenograft series, using double immunostaining and serial sectioning techniques. There were no significant differences in the expression of DPD and TS between AFP-positive group and -negative group. However, DPD was frequently co-expressed with AFP in poorly differentiated medullary areas of the AFP-positive gastric cancers. The data presented herein suggest that APAD should be sensitive to cisplatin, but resistant to capecitabine and 5′-deoxyfluorouridine, fluoropyrimidines which are converted to 5-fluorouracil by TP. S-1, a fluoropyrimidine containing a strong DPD inhibitor, may be effective for AFP-positive gastric cancers with poorly differentiated medullary growth pattern.

Original languageEnglish
Pages (from-to)721-727
Number of pages7
JournalOncology Reports
Volume16
Issue number4
Publication statusPublished - 2006 Oct
Externally publishedYes

Fingerprint

Fetal Proteins
Thymidine Phosphorylase
Adenocarcinoma
Dihydrouracil Dehydrogenase (NADP)
Metallothionein
Stomach Neoplasms
Heterografts
Neoplasms
Proteins
Thymidylate Synthase
Cisplatin
Biliary Tract
Fluorouracil
Phenotype
Drug Therapy

Keywords

  • α-fetoprotein
  • Cisplatin
  • Fluoropyrimidine
  • Metallothionein
  • Thymidine phosphorylase

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kamoshida, S., Suzuki, M., Sakurai, Y., Ochiai, M., Kimura, F., Kuwao, S., ... Tsutsumi, Y. (2006). Expression of chemoresistance-related proteins in α-fetoprotein- producing adenocarcinoma of the digestive organs. Oncology Reports, 16(4), 721-727.

Expression of chemoresistance-related proteins in α-fetoprotein- producing adenocarcinoma of the digestive organs. / Kamoshida, Shingo; Suzuki, Mai; Sakurai, Yoichi; Ochiai, Masahiro; Kimura, Fumikazu; Kuwao, Sadahito; Sakamoto, Kazuki; Sugimoto, Yoshikazu; Fukushima, Masakazu; Tsutsumi, Yutaka.

In: Oncology Reports, Vol. 16, No. 4, 10.2006, p. 721-727.

Research output: Contribution to journalArticle

Kamoshida, S, Suzuki, M, Sakurai, Y, Ochiai, M, Kimura, F, Kuwao, S, Sakamoto, K, Sugimoto, Y, Fukushima, M & Tsutsumi, Y 2006, 'Expression of chemoresistance-related proteins in α-fetoprotein- producing adenocarcinoma of the digestive organs', Oncology Reports, vol. 16, no. 4, pp. 721-727.
Kamoshida S, Suzuki M, Sakurai Y, Ochiai M, Kimura F, Kuwao S et al. Expression of chemoresistance-related proteins in α-fetoprotein- producing adenocarcinoma of the digestive organs. Oncology Reports. 2006 Oct;16(4):721-727.
Kamoshida, Shingo ; Suzuki, Mai ; Sakurai, Yoichi ; Ochiai, Masahiro ; Kimura, Fumikazu ; Kuwao, Sadahito ; Sakamoto, Kazuki ; Sugimoto, Yoshikazu ; Fukushima, Masakazu ; Tsutsumi, Yutaka. / Expression of chemoresistance-related proteins in α-fetoprotein- producing adenocarcinoma of the digestive organs. In: Oncology Reports. 2006 ; Vol. 16, No. 4. pp. 721-727.
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abstract = "α-fetoprotein-producing adenocarcinoma of the digestive organs (APAD) is known to show a poor prognosis. To clarify the characteristics of chemoresistance in APAD, three proteins of fluoropyrimidine chemotherapy association [dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and thymidylate synthase (TS)] and one protein of cisplatin association [metallothionein (MT)] were immuno-histochemically evaluated. Tissue samples were taken from 12 AFP-positive gastric cancers and 94 AFP-negative gastric cancers. Four AFP-positive cancer xenografts (one colonic, two pancreatic, and one biliary tract) and 17 AFP-negative cancer xenografts were also examined. In gastric cancers, high expression of TP was observed in 30{\%} of AFP-negative tumors but in none of AFP-positive tumors (p=0.03). High expression of MT was found in 30{\%} of AFP-negative tumors but in only one of the AFP-positive tumors. The TP-low and MT-low phenotype was noted in 92{\%} of AFP-positive tumors and in 46{\%} of AFP-negative tumors (p=0.004). None of the AFP-positive cancer xenografts revealed high TP expression and only one showed high MT expression. In the cellular level, TP and MT were scarcely co-expressed with AFP in either gastric cancer or xenograft series, using double immunostaining and serial sectioning techniques. There were no significant differences in the expression of DPD and TS between AFP-positive group and -negative group. However, DPD was frequently co-expressed with AFP in poorly differentiated medullary areas of the AFP-positive gastric cancers. The data presented herein suggest that APAD should be sensitive to cisplatin, but resistant to capecitabine and 5′-deoxyfluorouridine, fluoropyrimidines which are converted to 5-fluorouracil by TP. S-1, a fluoropyrimidine containing a strong DPD inhibitor, may be effective for AFP-positive gastric cancers with poorly differentiated medullary growth pattern.",
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