Would intratumor heterogeneity and specimen type affect metabolic assessment of breast cancer?

Abstract

Purpose : To determine whether biospecimen variables including intratumor spatial heterogeneity (center or periphery) and biospecimen type (in vivo collection of core biopsy samples or ex vivo collection of surgical tumor samples) affect the metabolic characterization of breast cancer assessed by HR-MAS MR spectroscopy, and identify any correlations between HR-MAS MR spectroscopy data and histologic prognostic factors in breast cancer patients.

Materials and Methods : This prospective study was approved by the institutional review board and informed

consent was obtained. Between July 2014 and January 2015, 35 patients with

invasive breast cancer who underwent surgery were initially included. In vivo core needle biopsy (CNB) specimens were obtained from 28 patients and two tissue samples were later obtained from the center and/or periphery of surgical tumor specimens in all 35 patients. After excluding samples without tumor cells, 4 patients with only one specimen were further excluded. Finally, 87 tissue samples from 31 patients were included and high resolution magic angle spinning (HR-MAS) magnetic resonance (MR) spectroscopy was performed. HR-MAS MR spectroscopic values were compared according to specimen type and histopathologic prognostic factors. Multivariate analysis of HR-MAS MR spectral data was also performed to visually assess variation among each patient in metabolic profiles according to specimen type.

Results : There was a moderate to substantial agreement between most of the HR-MAS MR spectroscopy data among all three specimen types (83.3%, 10 of 12 metabolites), between in vivo CNB and central surgical tumor samples (75.0%, 9 of 12), and between central and peripheral surgical tumor samples (91.7%, 11 of 12). However, PC concentrations did not correlate between CNB and central surgical specimens and between central and peripheral surgical specimens. In addition, glutamate concentrations did not correlate between CNB and central surgical specimens. In core needle biopsy samples, we found that the poor prognosis group showed significantly higher concentrations of Ala, glutamate, Gly, lactate and taurine than those of the good prognosis group. In central surgical tumor samples, tumors with a high nuclear grade showed lower concentrations of Cr and triple negative tumors showed lower concentrations of glutamine and taurine. In addition, concentrations of choline were higher in tumors larger than 2 cm or in those of the poor prognosis group. Most of the specimens from each patient were clustered together within one quadrant of the OPLS-DA score plot.

Conclusion : Most HR-MAS MR spectroscopic values studied do not have significant intratumor spatial heterogeneity or differ according to biospecimen type. However, PC and glutamate measurements may be affected by intratumor spatial location or biospecimen type. Further validation through future studies is needed for clinical implementation of these biomarkers based on data from a single tissue-biopsy sample.