Predicting metastatic risk of gastrointestinal stromal tumors

Role of cell proliferation and cell cycle regulatory proteins

Angel Panizo-Santos, Iosu Sola, Francisco Vega, Enrique De Alava, María Dolores Lozano, Miguel Angel Idoate, Javier Pardo-Mindán

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Gastrointestinal stromal tumors (GIST) are a heterogeneous group of neoplasms whose biologic behavior is difficult to predict. The aim of this study is to evaluate the prognostic value in GIST of some oncoproteins involved in regulation of cell proliferation. Tumor size, mitosis, necrosis, and p53, c-myc, and bcl-2 protein expression of 32 GIST were studied. Proliferative index was assessed with Ki67. The 32 cases were grouped into the following clinical categories: (1) clinically benign (BN) were defined as disease-free survival greater than 3 years (n=10); (2) clinically malignant (MN) in which local recurrence or metastasis occurred regardless of the follow-up time (n=15); and (3) clinically indeterminate (ID) owing to follow- up <3 years without metastasis or local recurrence (n=seven). Discriminant analysis was used to allocate any tumor to one of the two prognostic groups (BN or MN). In univariate analysis all six factors studied above proved to be of significant prognostic value. Using a multivariate stepwise discriminant analysis to take into account the interrelationship between factors, we found that c-myc expression was the most important prognostic factor, followed, in order of statistical weight, by size and Ki67. These were combined to define a discriminant score ([10.75 x c-myc]+[0.39 x size]+[0.078 x Ki67]- 15.54=score), which was capable of correctly identifying tumors in our series whose known clinical behavior was BN or MN in 92% of the cases. The classification score was applied subsequently to the seven clinically ID cases: Three (42.9%) were predicted as BN, and four (57.1%) were predicted as MN. Both expression of oncoprotein c-myc and the proliferative index provide prognostic information in GIST, in addition to morphologically established prognostic factors such as size. These factors in a discriminant analysis proved to be useful for the clinical classification of GIST into BN or MN and to predict the clinical outcome of clinically ID tumors.

Original languageEnglish
Pages (from-to)133-144
Number of pages12
JournalInternational Journal of Surgical Pathology
Volume8
Issue number2
StatePublished - Apr 1 2000
Externally publishedYes

Fingerprint

Cell Cycle Proteins
Gastrointestinal Stromal Tumors
Cell Proliferation
Discriminant Analysis
Oncogene Proteins
Neoplasms
Proto-Oncogene Proteins c-bcl-2
Neoplasm Metastasis
Recurrence
Mitosis
Disease-Free Survival
Necrosis
Weights and Measures

Keywords

  • Gastrointestinal stromal tumors
  • Immunohistochemistry
  • Oncoproteins
  • Prognosis

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine
  • Surgery

Cite this

Panizo-Santos, A., Sola, I., Vega, F., De Alava, E., Lozano, M. D., Idoate, M. A., & Pardo-Mindán, J. (2000). Predicting metastatic risk of gastrointestinal stromal tumors: Role of cell proliferation and cell cycle regulatory proteins. International Journal of Surgical Pathology, 8(2), 133-144.

Predicting metastatic risk of gastrointestinal stromal tumors : Role of cell proliferation and cell cycle regulatory proteins. / Panizo-Santos, Angel; Sola, Iosu; Vega, Francisco; De Alava, Enrique; Lozano, María Dolores; Idoate, Miguel Angel; Pardo-Mindán, Javier.

In: International Journal of Surgical Pathology, Vol. 8, No. 2, 01.04.2000, p. 133-144.

Research output: Contribution to journalArticle

Panizo-Santos, A, Sola, I, Vega, F, De Alava, E, Lozano, MD, Idoate, MA & Pardo-Mindán, J 2000, 'Predicting metastatic risk of gastrointestinal stromal tumors: Role of cell proliferation and cell cycle regulatory proteins', International Journal of Surgical Pathology, vol. 8, no. 2, pp. 133-144.
Panizo-Santos, Angel ; Sola, Iosu ; Vega, Francisco ; De Alava, Enrique ; Lozano, María Dolores ; Idoate, Miguel Angel ; Pardo-Mindán, Javier. / Predicting metastatic risk of gastrointestinal stromal tumors : Role of cell proliferation and cell cycle regulatory proteins. In: International Journal of Surgical Pathology. 2000 ; Vol. 8, No. 2. pp. 133-144.
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