DNA level and stereologic estimates of nuclear volume in squamous cell carcinomas of the uterine cervix. A comparative study with analysis of prognostic impact

Abstract

Grading of malignancy in squamous cell carcinomas of the uterine cervix is based on qualitative, morphologic examination and suffers from poor reproducibility. Using modern stereology, unbiased estimates of the three‐dimensional, volume‐weighted mean nuclear volume (nuclear v̄Mv), were obtained in pretreatment biopsies from 51 patients treated for cervical cancer in clinical Stages I through III (mean age of 56 years, follow‐up period >5 years). In addition, conventional, two‐dimensional morphometric estimates of nuclear and mitotic features were obtained. DNA indices (DI) were estimated by flow cytometry. Finally, the semiquantitative malignancy grade score value (MGS) was determined according to previously published methods. Estimates of nuclear v̄Mv were on average increased in euploid lesions (2P = 0.01), but the overall relationship between nuclear v̄Mv and DI was poor. Different clinical stages of disease did not differ with regard to nuclear v̄Mv (2P = 0.99) and DI (2P = 0.56). No relationship was disclosed between MGS and nuclear v̄Mv (2P = 0.85). Single‐factor analysis showed prognostic impact of clinical stage of disease (2P = 0.0001) and DI (2P = 0.04), whereas estimates of nuclear v̄Mv were only of marginal prognostic significance (2P = 0.07). How‐ M ever, Cox multivariate regression analysis showed independent prognostic value of patient age and nuclear v̄Mv along with clinical stage and DI. All other investigated variables were rejected from the model. A prognostic index with highly distinguishing capacity between prognostically poor and favorable cases was constructed (2P = 1.9 × 10−7). It is concluded that realistic estimates of nuclear volume are independent of nuclear DNA content and are of prognostic value for objective malignancy grading in patients with squamous cell carcinoma of the uterine cervix.

Nuclear size is sensitive to NTF2 protein levels in a manner dependent on Ran binding

“…Altered nuclear scaling is associated with many cancers, and cytopathologists monitor graded increases in nuclear size for cancer diagnosis and prognosis (Zink et al, 2004;Chow et al, 2012;. Importantly, nuclear size increases in cancer are frequently independent of gross ploidy changes (Lindberg, 1992;Miyamoto et al, 1992;Sørensen et al, 1992;Wang et al, 1992;Dangou et al, 1993;van Velthoven et al, 1995;Sørensen, 1996;Dey, 2010), implicating potential cytoplasmic contributions to altered nuclear size (Goehring and Hyman, 2012). It is unknown whether changes in nuclear size contribute to carcinogenesis, and answering this question necessitates an understanding of the mechanisms responsible for regulating nuclear size.…”

DNA Ploidy is Stronger Than Lymph Node Metastasis as Prognostic Factor in Cervical Carcinoma: 10-Year Results of a Prospective Study

“…3,4,6,8,10,14 The strength of our prospective study is that this is the first that presents 10-year results of flow cytometric DNA analysis from fresh tumor samples. In fact, it is known that histograms from paraffin-embedded material are less accurate than those from fresh tissue.…”

“…Some studies showed that tumor ploidy, DNA index, and SPF, obtained by flow cytometry, are strong and independent prognostic parameters in comparison with standard pathologic factors. 3,4,6,8,10,14 Other studies did not confirm these results. 2,5,7,9,11Y13,15,16 These conflicting evidences hampered a wider diffusion of DNA ploidy determination as standard practice in cervical carcinoma.…”

Mean nuclear volume: a supplementary prognostic factor in endometrial cancer

“…An unbiased stereologic method has been developed for estimating the volume‐weighted MNV from histologic sections ( 11 ) . A significant correlation between the MNV and the survival has been demonstrated in patients with bladder carcinomas ( 14 ) , malignant melanomas ( 15 ) , squamous cell carcinomas of the uterine cervix ( 16 ) , breast cancer ( 17 ) and squamous cell carcinoma of the lung ( 18 ) . However, no correlation has been observed between the MNV and the survival of patients with epithelial ovarian cancer ( 19 ) .…”