SMAD4 levels and response to 5-fluorouracil in colorectal cancer

Pia Alhopuro, Hafid Alazzouzi, Heli Sammalkorpi, Veronica Davalos, Reijo Salovaara, Akseli Hemminki, Heikki J Järvinen, Jukka-Pekka Mecklin, Simo Schwartz, Lauri A Aaltonen, Diego Arango

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    "We have recently reported that low tumor levels of SMAD4, a key mediator of transforming growth factor-p superfamily signaling, can predict the probability of recurrence in patients with Dukes C colorectal cancer who had surgery as the only form of treatment. However, standard treatment for Dukes C colorectal cancer patients currently involves the administration of 5-fluorouracil (5-FU) based adjuvant chemotherapy after surgery. Approximately 30% to 40% of these patients present with recurrence and die within 5 years, and there is great need for markers capable of predicting poor prognosis after the combined surgery/adjuvant treatment. In this study, we evaluate the prognostic value of SMAD4 in patients treated with surgery and 5-FU-based adjuvant therapy. We used immunohistochemistry and quantitative real-time reverse transcription-PCR to measure the levels of SMAD4 protein and mRNA expression in the primary tumors and a number of lymph node metastases from a series of 75 Dukes C colorectal cancer patients with at least 6 years of follow-up. Patients with tumors expressing low levels of SMAD4 protein or m RNA showed significantly shorted disease-free and overall survival than patients with high tumor levels of SMAD4. The median survival of patients with low SMAD4 protein or mRNA tumor levels was 1.4 and 1.2 years, respectively, whereas patients with high SMAD4 tumor level had a median survival of > 9.3 years. In addition, the protein and mRNA levels of SMAD4 in lymph node metastases was significantly lower than in primary tumors (P = 0.006). In contrast, allelic imbalance in chromosome 18q21 was of no prognostic significance in these patients. In conclusion, low SMAD4 tumor levels identified a subset of patients with poor prognosis following surgery and 5-FU-based adjuvant therapy; therefore, these patients could be good candidates to receive combined treatment with additional chemotherapeutic agents such as CPT-11 and/or oxaliplatin."
    Original languageEnglish
    JournalClinical Cancer Research
    Volume11
    Issue number17
    Pages (from-to)6311-6316
    Number of pages6
    ISSN1078-0432
    DOIs
    Publication statusPublished - 2005
    MoE publication typeA1 Journal article-refereed

    Fields of Science

    • 311 Basic medicine

    Cite this

    Alhopuro, P., Alazzouzi, H., Sammalkorpi, H., Davalos, V., Salovaara, R., Hemminki, A., ... Arango, D. (2005). SMAD4 levels and response to 5-fluorouracil in colorectal cancer. Clinical Cancer Research, 11(17), 6311-6316. https://doi.org/10.1158/1078-0432.CCR-05-0244
    Alhopuro, Pia ; Alazzouzi, Hafid ; Sammalkorpi, Heli ; Davalos, Veronica ; Salovaara, Reijo ; Hemminki, Akseli ; Järvinen, Heikki J ; Mecklin, Jukka-Pekka ; Schwartz, Simo ; Aaltonen, Lauri A ; Arango, Diego. / SMAD4 levels and response to 5-fluorouracil in colorectal cancer. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 17. pp. 6311-6316.
    @article{8e881f097a564d5b9bb0a20ba6edd135,
    title = "SMAD4 levels and response to 5-fluorouracil in colorectal cancer",
    abstract = "{"}We have recently reported that low tumor levels of SMAD4, a key mediator of transforming growth factor-p superfamily signaling, can predict the probability of recurrence in patients with Dukes C colorectal cancer who had surgery as the only form of treatment. However, standard treatment for Dukes C colorectal cancer patients currently involves the administration of 5-fluorouracil (5-FU) based adjuvant chemotherapy after surgery. Approximately 30{\%} to 40{\%} of these patients present with recurrence and die within 5 years, and there is great need for markers capable of predicting poor prognosis after the combined surgery/adjuvant treatment. In this study, we evaluate the prognostic value of SMAD4 in patients treated with surgery and 5-FU-based adjuvant therapy. We used immunohistochemistry and quantitative real-time reverse transcription-PCR to measure the levels of SMAD4 protein and mRNA expression in the primary tumors and a number of lymph node metastases from a series of 75 Dukes C colorectal cancer patients with at least 6 years of follow-up. Patients with tumors expressing low levels of SMAD4 protein or m RNA showed significantly shorted disease-free and overall survival than patients with high tumor levels of SMAD4. The median survival of patients with low SMAD4 protein or mRNA tumor levels was 1.4 and 1.2 years, respectively, whereas patients with high SMAD4 tumor level had a median survival of > 9.3 years. In addition, the protein and mRNA levels of SMAD4 in lymph node metastases was significantly lower than in primary tumors (P = 0.006). In contrast, allelic imbalance in chromosome 18q21 was of no prognostic significance in these patients. In conclusion, low SMAD4 tumor levels identified a subset of patients with poor prognosis following surgery and 5-FU-based adjuvant therapy; therefore, these patients could be good candidates to receive combined treatment with additional chemotherapeutic agents such as CPT-11 and/or oxaliplatin.{"}",
    keywords = "311 Basic medicine",
    author = "Pia Alhopuro and Hafid Alazzouzi and Heli Sammalkorpi and Veronica Davalos and Reijo Salovaara and Akseli Hemminki and J{\"a}rvinen, {Heikki J} and Jukka-Pekka Mecklin and Simo Schwartz and Aaltonen, {Lauri A} and Diego Arango",
    year = "2005",
    doi = "10.1158/1078-0432.CCR-05-0244",
    language = "English",
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    Alhopuro, P, Alazzouzi, H, Sammalkorpi, H, Davalos, V, Salovaara, R, Hemminki, A, Järvinen, HJ, Mecklin, J-P, Schwartz, S, Aaltonen, LA & Arango, D 2005, 'SMAD4 levels and response to 5-fluorouracil in colorectal cancer', Clinical Cancer Research, vol. 11, no. 17, pp. 6311-6316. https://doi.org/10.1158/1078-0432.CCR-05-0244

    SMAD4 levels and response to 5-fluorouracil in colorectal cancer. / Alhopuro, Pia; Alazzouzi, Hafid; Sammalkorpi, Heli; Davalos, Veronica; Salovaara, Reijo; Hemminki, Akseli; Järvinen, Heikki J; Mecklin, Jukka-Pekka; Schwartz, Simo; Aaltonen, Lauri A; Arango, Diego.

    In: Clinical Cancer Research, Vol. 11, No. 17, 2005, p. 6311-6316.

    Research output: Contribution to journalArticleScientificpeer-review

    TY - JOUR

    T1 - SMAD4 levels and response to 5-fluorouracil in colorectal cancer

    AU - Alhopuro, Pia

    AU - Alazzouzi, Hafid

    AU - Sammalkorpi, Heli

    AU - Davalos, Veronica

    AU - Salovaara, Reijo

    AU - Hemminki, Akseli

    AU - Järvinen, Heikki J

    AU - Mecklin, Jukka-Pekka

    AU - Schwartz, Simo

    AU - Aaltonen, Lauri A

    AU - Arango, Diego

    PY - 2005

    Y1 - 2005

    N2 - "We have recently reported that low tumor levels of SMAD4, a key mediator of transforming growth factor-p superfamily signaling, can predict the probability of recurrence in patients with Dukes C colorectal cancer who had surgery as the only form of treatment. However, standard treatment for Dukes C colorectal cancer patients currently involves the administration of 5-fluorouracil (5-FU) based adjuvant chemotherapy after surgery. Approximately 30% to 40% of these patients present with recurrence and die within 5 years, and there is great need for markers capable of predicting poor prognosis after the combined surgery/adjuvant treatment. In this study, we evaluate the prognostic value of SMAD4 in patients treated with surgery and 5-FU-based adjuvant therapy. We used immunohistochemistry and quantitative real-time reverse transcription-PCR to measure the levels of SMAD4 protein and mRNA expression in the primary tumors and a number of lymph node metastases from a series of 75 Dukes C colorectal cancer patients with at least 6 years of follow-up. Patients with tumors expressing low levels of SMAD4 protein or m RNA showed significantly shorted disease-free and overall survival than patients with high tumor levels of SMAD4. The median survival of patients with low SMAD4 protein or mRNA tumor levels was 1.4 and 1.2 years, respectively, whereas patients with high SMAD4 tumor level had a median survival of > 9.3 years. In addition, the protein and mRNA levels of SMAD4 in lymph node metastases was significantly lower than in primary tumors (P = 0.006). In contrast, allelic imbalance in chromosome 18q21 was of no prognostic significance in these patients. In conclusion, low SMAD4 tumor levels identified a subset of patients with poor prognosis following surgery and 5-FU-based adjuvant therapy; therefore, these patients could be good candidates to receive combined treatment with additional chemotherapeutic agents such as CPT-11 and/or oxaliplatin."

    AB - "We have recently reported that low tumor levels of SMAD4, a key mediator of transforming growth factor-p superfamily signaling, can predict the probability of recurrence in patients with Dukes C colorectal cancer who had surgery as the only form of treatment. However, standard treatment for Dukes C colorectal cancer patients currently involves the administration of 5-fluorouracil (5-FU) based adjuvant chemotherapy after surgery. Approximately 30% to 40% of these patients present with recurrence and die within 5 years, and there is great need for markers capable of predicting poor prognosis after the combined surgery/adjuvant treatment. In this study, we evaluate the prognostic value of SMAD4 in patients treated with surgery and 5-FU-based adjuvant therapy. We used immunohistochemistry and quantitative real-time reverse transcription-PCR to measure the levels of SMAD4 protein and mRNA expression in the primary tumors and a number of lymph node metastases from a series of 75 Dukes C colorectal cancer patients with at least 6 years of follow-up. Patients with tumors expressing low levels of SMAD4 protein or m RNA showed significantly shorted disease-free and overall survival than patients with high tumor levels of SMAD4. The median survival of patients with low SMAD4 protein or mRNA tumor levels was 1.4 and 1.2 years, respectively, whereas patients with high SMAD4 tumor level had a median survival of > 9.3 years. In addition, the protein and mRNA levels of SMAD4 in lymph node metastases was significantly lower than in primary tumors (P = 0.006). In contrast, allelic imbalance in chromosome 18q21 was of no prognostic significance in these patients. In conclusion, low SMAD4 tumor levels identified a subset of patients with poor prognosis following surgery and 5-FU-based adjuvant therapy; therefore, these patients could be good candidates to receive combined treatment with additional chemotherapeutic agents such as CPT-11 and/or oxaliplatin."

    KW - 311 Basic medicine

    U2 - 10.1158/1078-0432.CCR-05-0244

    DO - 10.1158/1078-0432.CCR-05-0244

    M3 - Article

    VL - 11

    SP - 6311

    EP - 6316

    JO - Clinical Cancer Research

    JF - Clinical Cancer Research

    SN - 1078-0432

    IS - 17

    ER -