Correlation of CHEK2 protein expression and c.1100delC mutation status with tumor characteristics among unselected breast cancer patients

Outi Kilpivaara, Jirina Bartkova, Hannaleena Eerola, Kirsi Syrjäkoski, Pia Vahteristo, Jiri Lukas, Carl Blomqvist, Kaija Holli, Päivi Heikkilä, Guido Sauter, Olli Kallioniemi, Jiri Bartek, Heli Nevanlinna (Corresponding Author)

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Abstract

The CHEK2 kinase is a tumor suppressor whose activation in response to DNA double‐strand breaks contributes to cell cycle arrest or apoptosis. The c.1100delC mutation is associated with familial breast cancer, and tumors from mutation carriers show reduced or absent CHEK2 protein expression. We have here studied CHEK2 protein expression by immunohistochemistry on a tissue microarray of 611 unselected breast tumors and also evaluated the tumor characteristics among 1,297 unselected breast cancer patients defined for the c.1100delC germ line mutation status (2.5% carrier frequency). CHEK2 protein expression was reduced in 21.1% of the unselected breast cancers studied. Tumors with reduced CHEK2 expression had more often larger primary tumor size (pT3–4; nominal significance p = 0.002) compared to tumors with normal staining. A similar trend for larger tumor size was seen among the 37 breast tumors from c.1100delC germ line mutation carriers. Tumors from c.1100delC mutation carriers were of higher grade than those of noncarriers (nominal significance p = 0.02). The c.1100delC germ line mutation also associated strongly with bilateral breast cancer. No significant correlation was seen between CHEK2 status and hormone receptor status, histology, lymph node status, or overall survival.
Original languageEnglish
Pages (from-to)575 - 580
Number of pages6
JournalInternational Journal of Cancer
Volume113
Issue number4
DOIs
Publication statusPublished - 2005
MoE publication typeA1 Journal article-refereed

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Breast Neoplasms
Mutation
Germ-Line Mutation
Neoplasms
Proteins
Checkpoint Kinase 2
DNA Breaks
Cell Cycle Checkpoints
Histology
Lymph Nodes
Immunohistochemistry
Hormones
Apoptosis
Staining and Labeling
Survival

Keywords

  • CHEK2
  • tumor characteristics
  • breast cancer

Cite this

Kilpivaara, O., Bartkova, J., Eerola, H., Syrjäkoski, K., Vahteristo, P., Lukas, J., ... Nevanlinna, H. (2005). Correlation of CHEK2 protein expression and c.1100delC mutation status with tumor characteristics among unselected breast cancer patients. International Journal of Cancer, 113(4), 575 - 580. https://doi.org/10.1002/ijc.20638
Kilpivaara, Outi ; Bartkova, Jirina ; Eerola, Hannaleena ; Syrjäkoski, Kirsi ; Vahteristo, Pia ; Lukas, Jiri ; Blomqvist, Carl ; Holli, Kaija ; Heikkilä, Päivi ; Sauter, Guido ; Kallioniemi, Olli ; Bartek, Jiri ; Nevanlinna, Heli. / Correlation of CHEK2 protein expression and c.1100delC mutation status with tumor characteristics among unselected breast cancer patients. In: International Journal of Cancer. 2005 ; Vol. 113, No. 4. pp. 575 - 580.
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abstract = "The CHEK2 kinase is a tumor suppressor whose activation in response to DNA double‐strand breaks contributes to cell cycle arrest or apoptosis. The c.1100delC mutation is associated with familial breast cancer, and tumors from mutation carriers show reduced or absent CHEK2 protein expression. We have here studied CHEK2 protein expression by immunohistochemistry on a tissue microarray of 611 unselected breast tumors and also evaluated the tumor characteristics among 1,297 unselected breast cancer patients defined for the c.1100delC germ line mutation status (2.5{\%} carrier frequency). CHEK2 protein expression was reduced in 21.1{\%} of the unselected breast cancers studied. Tumors with reduced CHEK2 expression had more often larger primary tumor size (pT3–4; nominal significance p = 0.002) compared to tumors with normal staining. A similar trend for larger tumor size was seen among the 37 breast tumors from c.1100delC germ line mutation carriers. Tumors from c.1100delC mutation carriers were of higher grade than those of noncarriers (nominal significance p = 0.02). The c.1100delC germ line mutation also associated strongly with bilateral breast cancer. No significant correlation was seen between CHEK2 status and hormone receptor status, histology, lymph node status, or overall survival.",
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Kilpivaara, O, Bartkova, J, Eerola, H, Syrjäkoski, K, Vahteristo, P, Lukas, J, Blomqvist, C, Holli, K, Heikkilä, P, Sauter, G, Kallioniemi, O, Bartek, J & Nevanlinna, H 2005, 'Correlation of CHEK2 protein expression and c.1100delC mutation status with tumor characteristics among unselected breast cancer patients', International Journal of Cancer, vol. 113, no. 4, pp. 575 - 580. https://doi.org/10.1002/ijc.20638

Correlation of CHEK2 protein expression and c.1100delC mutation status with tumor characteristics among unselected breast cancer patients. / Kilpivaara, Outi; Bartkova, Jirina; Eerola, Hannaleena; Syrjäkoski, Kirsi; Vahteristo, Pia; Lukas, Jiri; Blomqvist, Carl; Holli, Kaija; Heikkilä, Päivi; Sauter, Guido; Kallioniemi, Olli; Bartek, Jiri; Nevanlinna, Heli (Corresponding Author).

In: International Journal of Cancer, Vol. 113, No. 4, 2005, p. 575 - 580.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Correlation of CHEK2 protein expression and c.1100delC mutation status with tumor characteristics among unselected breast cancer patients

AU - Kilpivaara, Outi

AU - Bartkova, Jirina

AU - Eerola, Hannaleena

AU - Syrjäkoski, Kirsi

AU - Vahteristo, Pia

AU - Lukas, Jiri

AU - Blomqvist, Carl

AU - Holli, Kaija

AU - Heikkilä, Päivi

AU - Sauter, Guido

AU - Kallioniemi, Olli

AU - Bartek, Jiri

AU - Nevanlinna, Heli

PY - 2005

Y1 - 2005

N2 - The CHEK2 kinase is a tumor suppressor whose activation in response to DNA double‐strand breaks contributes to cell cycle arrest or apoptosis. The c.1100delC mutation is associated with familial breast cancer, and tumors from mutation carriers show reduced or absent CHEK2 protein expression. We have here studied CHEK2 protein expression by immunohistochemistry on a tissue microarray of 611 unselected breast tumors and also evaluated the tumor characteristics among 1,297 unselected breast cancer patients defined for the c.1100delC germ line mutation status (2.5% carrier frequency). CHEK2 protein expression was reduced in 21.1% of the unselected breast cancers studied. Tumors with reduced CHEK2 expression had more often larger primary tumor size (pT3–4; nominal significance p = 0.002) compared to tumors with normal staining. A similar trend for larger tumor size was seen among the 37 breast tumors from c.1100delC germ line mutation carriers. Tumors from c.1100delC mutation carriers were of higher grade than those of noncarriers (nominal significance p = 0.02). The c.1100delC germ line mutation also associated strongly with bilateral breast cancer. No significant correlation was seen between CHEK2 status and hormone receptor status, histology, lymph node status, or overall survival.

AB - The CHEK2 kinase is a tumor suppressor whose activation in response to DNA double‐strand breaks contributes to cell cycle arrest or apoptosis. The c.1100delC mutation is associated with familial breast cancer, and tumors from mutation carriers show reduced or absent CHEK2 protein expression. We have here studied CHEK2 protein expression by immunohistochemistry on a tissue microarray of 611 unselected breast tumors and also evaluated the tumor characteristics among 1,297 unselected breast cancer patients defined for the c.1100delC germ line mutation status (2.5% carrier frequency). CHEK2 protein expression was reduced in 21.1% of the unselected breast cancers studied. Tumors with reduced CHEK2 expression had more often larger primary tumor size (pT3–4; nominal significance p = 0.002) compared to tumors with normal staining. A similar trend for larger tumor size was seen among the 37 breast tumors from c.1100delC germ line mutation carriers. Tumors from c.1100delC mutation carriers were of higher grade than those of noncarriers (nominal significance p = 0.02). The c.1100delC germ line mutation also associated strongly with bilateral breast cancer. No significant correlation was seen between CHEK2 status and hormone receptor status, histology, lymph node status, or overall survival.

KW - CHEK2

KW - tumor characteristics

KW - breast cancer

U2 - 10.1002/ijc.20638

DO - 10.1002/ijc.20638

M3 - Article

VL - 113

SP - 575

EP - 580

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 4

ER -