Cathepsin E Is a Marker of Gastric Differentiation and Signet-Ring Cell Carcinoma of Stomach: A Novel Suggestion on Gastric Tumorigenesis

Maki Konno-Shimizu, Nobutake Yamamichi, Ken Ichi Inada, Natsuko Kageyama-Yahara, Kazuya Shiogama, Yu Takahashi, Itsuko Asada-Hirayama, Mitsue Yamamichi-Nishina, Chiemi Nakayama, Satoshi Ono, Shinya Kodashima, Mitsuhiro Fujishiro, Yutaka Tsutsumi, Masao Ichinose, Kazuhiko Koike

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Abstract

Gastric cancer (GC) presents various histological features, though the mechanism underlying its diversity is seldom elucidated. It is mainly classified into well differentiated tubular adenocarcinoma (tub1), moderately differentiated tubular adenocarcinoma (tub2), poorly differentiated adenocarcinoma (por), signet-ring cell carcinoma (sig), mucinous adenocarcinoma (muc), and papillary adenocarcinoma (pap). By screening, we found cathepsin E (CTSE) expresses universally in sig-type, occasionally in por-type, and rarely in tub1/tub2-type GC cell lines. In surgically-resected specimens, CTSE was immunostained in 50/51 sig-type (98.0%), 3/10 tub1-type (30.0%), 7/18 tub2-type (38.9%), 15/26 por-type (57.7%), 4/10 pap-type (40.0%), and 0/3 muc-type (0.0%) GC. In endoscopically-resected specimens, 6/7 sig-type (85.7%), 7/52 tub1-type (13.7%), 5/12 tub2-type (41.7%), 2/7 pap-type (28.6%) GC and 0/6 adenoma (0.0%) expressed CTSE. For non-malignant tissues, CTSE is universally expressed in normal fundic, pyloric, and cardiac glands of stomach, but hardly in other digestive organs. In the precancerous intestinal metaplasia of stomach, CTSE is mostly observed in mixed gastric-and-intestinal type and deficient in solely-intestinal type. CTSE expression is positively correlated with gastric marker MUC5AC (p<0.0001) and negatively correlated with intestinal marker MUC2 (p = 0.0019). For sig-type GC, in both tumors and background mucosa, expression of MUC5AC and CTSE is high whereas that of MUC2 is low, indicating that sig-type GC reflects the features of background mucosa. For gastric adenoma and tub1/tub2-type GC, more undifferentiated tumors tend to show higher expression of CTSE with MUC5AC and lower expression of MUC2 in tumors, but they tend to present lower expression of CTSE, MUC5AC and MUC2 in background mucosa. These suggest that more malignant gastric adenocarcinoma with stronger gastric and weaker intestinal properties tend to arise from background mucosa with decreased both gastric and intestinal features. In conclusion, CTSE is a marker of both gastric differentiation and signet-ring cell carcinoma, which should shed light on the mechanism of gastric tumorigenesis.

Original languageEnglish
Article numbere56766
JournalPloS one
Volume8
Issue number2
DOIs
Publication statusPublished - 22-02-2013

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cathepsin E
Cathepsin E
Signet Ring Cell Carcinoma
Differentiation Antigens
carcinogenesis
carcinoma
Stomach
stomach neoplasms
Carcinogenesis
stomach
Cells
Stomach Neoplasms
adenocarcinoma
mucosa
cells
Mucous Membrane
Adenocarcinoma
Tumors
gastric mucosa
adenoma

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Konno-Shimizu, Maki ; Yamamichi, Nobutake ; Inada, Ken Ichi ; Kageyama-Yahara, Natsuko ; Shiogama, Kazuya ; Takahashi, Yu ; Asada-Hirayama, Itsuko ; Yamamichi-Nishina, Mitsue ; Nakayama, Chiemi ; Ono, Satoshi ; Kodashima, Shinya ; Fujishiro, Mitsuhiro ; Tsutsumi, Yutaka ; Ichinose, Masao ; Koike, Kazuhiko. / Cathepsin E Is a Marker of Gastric Differentiation and Signet-Ring Cell Carcinoma of Stomach : A Novel Suggestion on Gastric Tumorigenesis. In: PloS one. 2013 ; Vol. 8, No. 2.
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title = "Cathepsin E Is a Marker of Gastric Differentiation and Signet-Ring Cell Carcinoma of Stomach: A Novel Suggestion on Gastric Tumorigenesis",
abstract = "Gastric cancer (GC) presents various histological features, though the mechanism underlying its diversity is seldom elucidated. It is mainly classified into well differentiated tubular adenocarcinoma (tub1), moderately differentiated tubular adenocarcinoma (tub2), poorly differentiated adenocarcinoma (por), signet-ring cell carcinoma (sig), mucinous adenocarcinoma (muc), and papillary adenocarcinoma (pap). By screening, we found cathepsin E (CTSE) expresses universally in sig-type, occasionally in por-type, and rarely in tub1/tub2-type GC cell lines. In surgically-resected specimens, CTSE was immunostained in 50/51 sig-type (98.0{\%}), 3/10 tub1-type (30.0{\%}), 7/18 tub2-type (38.9{\%}), 15/26 por-type (57.7{\%}), 4/10 pap-type (40.0{\%}), and 0/3 muc-type (0.0{\%}) GC. In endoscopically-resected specimens, 6/7 sig-type (85.7{\%}), 7/52 tub1-type (13.7{\%}), 5/12 tub2-type (41.7{\%}), 2/7 pap-type (28.6{\%}) GC and 0/6 adenoma (0.0{\%}) expressed CTSE. For non-malignant tissues, CTSE is universally expressed in normal fundic, pyloric, and cardiac glands of stomach, but hardly in other digestive organs. In the precancerous intestinal metaplasia of stomach, CTSE is mostly observed in mixed gastric-and-intestinal type and deficient in solely-intestinal type. CTSE expression is positively correlated with gastric marker MUC5AC (p<0.0001) and negatively correlated with intestinal marker MUC2 (p = 0.0019). For sig-type GC, in both tumors and background mucosa, expression of MUC5AC and CTSE is high whereas that of MUC2 is low, indicating that sig-type GC reflects the features of background mucosa. For gastric adenoma and tub1/tub2-type GC, more undifferentiated tumors tend to show higher expression of CTSE with MUC5AC and lower expression of MUC2 in tumors, but they tend to present lower expression of CTSE, MUC5AC and MUC2 in background mucosa. These suggest that more malignant gastric adenocarcinoma with stronger gastric and weaker intestinal properties tend to arise from background mucosa with decreased both gastric and intestinal features. In conclusion, CTSE is a marker of both gastric differentiation and signet-ring cell carcinoma, which should shed light on the mechanism of gastric tumorigenesis.",
author = "Maki Konno-Shimizu and Nobutake Yamamichi and Inada, {Ken Ichi} and Natsuko Kageyama-Yahara and Kazuya Shiogama and Yu Takahashi and Itsuko Asada-Hirayama and Mitsue Yamamichi-Nishina and Chiemi Nakayama and Satoshi Ono and Shinya Kodashima and Mitsuhiro Fujishiro and Yutaka Tsutsumi and Masao Ichinose and Kazuhiko Koike",
year = "2013",
month = "2",
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doi = "10.1371/journal.pone.0056766",
language = "English",
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Konno-Shimizu, M, Yamamichi, N, Inada, KI, Kageyama-Yahara, N, Shiogama, K, Takahashi, Y, Asada-Hirayama, I, Yamamichi-Nishina, M, Nakayama, C, Ono, S, Kodashima, S, Fujishiro, M, Tsutsumi, Y, Ichinose, M & Koike, K 2013, 'Cathepsin E Is a Marker of Gastric Differentiation and Signet-Ring Cell Carcinoma of Stomach: A Novel Suggestion on Gastric Tumorigenesis', PloS one, vol. 8, no. 2, e56766. https://doi.org/10.1371/journal.pone.0056766

Cathepsin E Is a Marker of Gastric Differentiation and Signet-Ring Cell Carcinoma of Stomach : A Novel Suggestion on Gastric Tumorigenesis. / Konno-Shimizu, Maki; Yamamichi, Nobutake; Inada, Ken Ichi; Kageyama-Yahara, Natsuko; Shiogama, Kazuya; Takahashi, Yu; Asada-Hirayama, Itsuko; Yamamichi-Nishina, Mitsue; Nakayama, Chiemi; Ono, Satoshi; Kodashima, Shinya; Fujishiro, Mitsuhiro; Tsutsumi, Yutaka; Ichinose, Masao; Koike, Kazuhiko.

In: PloS one, Vol. 8, No. 2, e56766, 22.02.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cathepsin E Is a Marker of Gastric Differentiation and Signet-Ring Cell Carcinoma of Stomach

T2 - A Novel Suggestion on Gastric Tumorigenesis

AU - Konno-Shimizu, Maki

AU - Yamamichi, Nobutake

AU - Inada, Ken Ichi

AU - Kageyama-Yahara, Natsuko

AU - Shiogama, Kazuya

AU - Takahashi, Yu

AU - Asada-Hirayama, Itsuko

AU - Yamamichi-Nishina, Mitsue

AU - Nakayama, Chiemi

AU - Ono, Satoshi

AU - Kodashima, Shinya

AU - Fujishiro, Mitsuhiro

AU - Tsutsumi, Yutaka

AU - Ichinose, Masao

AU - Koike, Kazuhiko

PY - 2013/2/22

Y1 - 2013/2/22

N2 - Gastric cancer (GC) presents various histological features, though the mechanism underlying its diversity is seldom elucidated. It is mainly classified into well differentiated tubular adenocarcinoma (tub1), moderately differentiated tubular adenocarcinoma (tub2), poorly differentiated adenocarcinoma (por), signet-ring cell carcinoma (sig), mucinous adenocarcinoma (muc), and papillary adenocarcinoma (pap). By screening, we found cathepsin E (CTSE) expresses universally in sig-type, occasionally in por-type, and rarely in tub1/tub2-type GC cell lines. In surgically-resected specimens, CTSE was immunostained in 50/51 sig-type (98.0%), 3/10 tub1-type (30.0%), 7/18 tub2-type (38.9%), 15/26 por-type (57.7%), 4/10 pap-type (40.0%), and 0/3 muc-type (0.0%) GC. In endoscopically-resected specimens, 6/7 sig-type (85.7%), 7/52 tub1-type (13.7%), 5/12 tub2-type (41.7%), 2/7 pap-type (28.6%) GC and 0/6 adenoma (0.0%) expressed CTSE. For non-malignant tissues, CTSE is universally expressed in normal fundic, pyloric, and cardiac glands of stomach, but hardly in other digestive organs. In the precancerous intestinal metaplasia of stomach, CTSE is mostly observed in mixed gastric-and-intestinal type and deficient in solely-intestinal type. CTSE expression is positively correlated with gastric marker MUC5AC (p<0.0001) and negatively correlated with intestinal marker MUC2 (p = 0.0019). For sig-type GC, in both tumors and background mucosa, expression of MUC5AC and CTSE is high whereas that of MUC2 is low, indicating that sig-type GC reflects the features of background mucosa. For gastric adenoma and tub1/tub2-type GC, more undifferentiated tumors tend to show higher expression of CTSE with MUC5AC and lower expression of MUC2 in tumors, but they tend to present lower expression of CTSE, MUC5AC and MUC2 in background mucosa. These suggest that more malignant gastric adenocarcinoma with stronger gastric and weaker intestinal properties tend to arise from background mucosa with decreased both gastric and intestinal features. In conclusion, CTSE is a marker of both gastric differentiation and signet-ring cell carcinoma, which should shed light on the mechanism of gastric tumorigenesis.

AB - Gastric cancer (GC) presents various histological features, though the mechanism underlying its diversity is seldom elucidated. It is mainly classified into well differentiated tubular adenocarcinoma (tub1), moderately differentiated tubular adenocarcinoma (tub2), poorly differentiated adenocarcinoma (por), signet-ring cell carcinoma (sig), mucinous adenocarcinoma (muc), and papillary adenocarcinoma (pap). By screening, we found cathepsin E (CTSE) expresses universally in sig-type, occasionally in por-type, and rarely in tub1/tub2-type GC cell lines. In surgically-resected specimens, CTSE was immunostained in 50/51 sig-type (98.0%), 3/10 tub1-type (30.0%), 7/18 tub2-type (38.9%), 15/26 por-type (57.7%), 4/10 pap-type (40.0%), and 0/3 muc-type (0.0%) GC. In endoscopically-resected specimens, 6/7 sig-type (85.7%), 7/52 tub1-type (13.7%), 5/12 tub2-type (41.7%), 2/7 pap-type (28.6%) GC and 0/6 adenoma (0.0%) expressed CTSE. For non-malignant tissues, CTSE is universally expressed in normal fundic, pyloric, and cardiac glands of stomach, but hardly in other digestive organs. In the precancerous intestinal metaplasia of stomach, CTSE is mostly observed in mixed gastric-and-intestinal type and deficient in solely-intestinal type. CTSE expression is positively correlated with gastric marker MUC5AC (p<0.0001) and negatively correlated with intestinal marker MUC2 (p = 0.0019). For sig-type GC, in both tumors and background mucosa, expression of MUC5AC and CTSE is high whereas that of MUC2 is low, indicating that sig-type GC reflects the features of background mucosa. For gastric adenoma and tub1/tub2-type GC, more undifferentiated tumors tend to show higher expression of CTSE with MUC5AC and lower expression of MUC2 in tumors, but they tend to present lower expression of CTSE, MUC5AC and MUC2 in background mucosa. These suggest that more malignant gastric adenocarcinoma with stronger gastric and weaker intestinal properties tend to arise from background mucosa with decreased both gastric and intestinal features. In conclusion, CTSE is a marker of both gastric differentiation and signet-ring cell carcinoma, which should shed light on the mechanism of gastric tumorigenesis.

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