BACKGROUND: The incidence and significance of tumor heterogeneity in primary tumors and metastatic lymph nodes were investigated in Stage IB-IIA cervical cancers. METHODS: Paraffin-embedded tissues from 96 radical hysterectomy specimens were dewaxed, disaggregated, and subjected to dual parameter flow cytometry. Three-dimensional histograms were generated to delineate different tumor populations. A DNA index difference of at least +/- 0.15 was used to define tumor heterogeneity. RESULTS: Mean DNA index difference of various tumor populations was 0.29 +/- 0.13. Among 69 patients with normal lymph nodes, there were 12 patients (incidence, 17.4%) with tumor heterogeneity in the primary tumors. Of 27 patients with metastatic lymph nodes, 5 (incidence, 18.5%) had evidence of tumor heterogeneity in the primary tumor, and 18 of 47 (incidence, 38.3%) had tumor heterogeneity in metastatic lymph nodes. When using DNA index to determine clonal origin of metastatic lymph nodes, as many as 60% of the metastases could not be traced to the primary tumor. Tumor heterogeneity was associated with a 40% reduction in median survival time. However, because of the small number of patients with tumor heterogeneity, statistical analyses did not show prognostic significance. CONCLUSIONS: Tumor heterogeneity appeared to be a common characteristic of early cervical carcinoma. Additional study is needed to fully evaluate its prognostic value.
BACKGROUND: The incidence and significance of tumor heterogeneity in primary tumors and metastatic lymph nodes were investigated in Stage IB-IIA cervical cancers. METHODS:Paraffin-embedded tissues from 96 radical hysterectomy specimens were dewaxed, disaggregated, and subjected to dual parameter flow cytometry. Three-dimensional histograms were generated to delineate different tumor populations. A DNA index difference of at least +/- 0.15 was used to define tumor heterogeneity. RESULTS: Mean DNA index difference of various tumor populations was 0.29 +/- 0.13. Among 69 patients with normal lymph nodes, there were 12 patients (incidence, 17.4%) with tumor heterogeneity in the primary tumors. Of 27 patients with metastatic lymph nodes, 5 (incidence, 18.5%) had evidence of tumor heterogeneity in the primary tumor, and 18 of 47 (incidence, 38.3%) had tumor heterogeneity in metastatic lymph nodes. When using DNA index to determine clonal origin of metastatic lymph nodes, as many as 60% of the metastases could not be traced to the primary tumor. Tumor heterogeneity was associated with a 40% reduction in median survival time. However, because of the small number of patients with tumor heterogeneity, statistical analyses did not show prognostic significance. CONCLUSIONS:Tumor heterogeneity appeared to be a common characteristic of early cervical carcinoma. Additional study is needed to fully evaluate its prognostic value.
Authors: Christine How; Melania Pintilie; Jeff P Bruce; Angela B Y Hui; Blaise A Clarke; Philip Wong; Shaoming Yin; Rui Yan; Daryl Waggott; Paul C Boutros; Anthony Fyles; David W Hedley; Richard P Hill; Michael Milosevic; Fei-Fei Liu Journal: PLoS One Date: 2015-04-16 Impact factor: 3.240