Evolution in endometrial cancer: evidence from an immunohistochemical study.

Abstract

BACKGROUND:

It is poorly described how endometrial cancer biology changes during tumor evolution. We hypothesize that characterization of molecular targets in recurrent lesions is more relevant for targeting treatment.

METHODS:

Paired biopsies from primary and recurrent endometrial cancer tumors (n = 85) were stained immunohistochemically for the following proteins: estrogen receptor (ER), progesterone receptor (PR), stathmin (correlating with phosphatidylinositol 3-kinase activity), HER-2/neu, WT1 (Wilms tumor gene 1), phospho-mammalian target of rapamycin (p-mTOR), and p53. Each tumor was scored, using a semiquantitative and subjective grading system. Discordance, a change in expression between primary and recurrent tumor, was defined as ≥ 2 step change; concordance was ≤ 1 step change. The frequency of change was correlated with established prognostic markers in endometrial cancer.

RESULTS:

Fifty-six patients (67%) were diagnosed with endometrioid carcinoma, 23 (27%) with serous/clear cell carcinoma. A change in expression between primary and recurrent tumor was noted in 7% to 31% of patients for ER, PR, stathmin, HER-2/neu, WT1, p-mTOR, and p53. Concordant-positive cases for PR were significantly correlated with stage, tumor grade, and histological subtype. Expression of ER, p53, and p-mTOR in cytoplasm in the recurrent tumor correlated significantly with survival.

CONCLUSIONS:

Endometrial cancer biology changes over time. The decision on targeted treatment should preferably be based on recurrent tumor characteristics.

• Authors: Ingrid Vandenput, Jone Trovik, Karin Leunen, Elisabeth Wik, Ingunn Stefansson, Lars Akslen, Philippe Moerman, Ignace Vergote, Helga Salvesen, Frédéric Amant
• Journal: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society (Int J Gynecol Cancer) Vol. 21 Issue 2 Pg. 316-22 (Feb 2011) ISSN: 1525-1438 [Electronic] England
• PMID: 21734474 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Estrogen Receptor alpha
• Receptors, Progesterone
• Stathmin
• Tumor Suppressor Protein p53
• WT1 Proteins
• MTOR protein, human
• ERBB2 protein, human
• Receptor, ErbB-2
• TOR Serine-Threonine Kinases

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (metabolism)
• Biopsy
• Endometrial Neoplasms (metabolism, mortality, pathology)
• Endometrium (pathology)
• Estrogen Receptor alpha (metabolism)
• Female
• Humans
• Immunohistochemistry
• Middle Aged
• Neoplasm Recurrence, Local (metabolism, mortality, pathology)
• Protein Array Analysis
• Receptor, ErbB-2 (metabolism)
• Receptors, Progesterone (metabolism)
• Retrospective Studies
• Stathmin (biosynthesis)
• Survival Analysis
• TOR Serine-Threonine Kinases (metabolism)
• Tumor Suppressor Protein p53 (metabolism)
• WT1 Proteins (metabolism)