The Fractal Dimension Suggests Two Chromatin Configurations in Small Cell Neuroendocrine Lung Cancer and Is an Independent Unfavorable Prognostic Factor for Overall Survival

Experimental studies have shown that in small cell neuroendocrine lung carcinomas (SCLC) global opening of the chromatin structure is associated with a higher transcription activity and increase of tumor aggressiveness and metastasis. The study of the fractal characteristics (FD) of nuclear chromatin has been widely used to describe the cell nuclear texture and its changes correspond to changes in nuclear metabolic and transcription activity. Hence, we investigated whether the nuclear fractal dimension could be a prognostic factor in SCLC. Hematoxylin-eosin stained brush cytology slides from 49 patients with SCLC were retrieved from our files. The chromatin (FD) was calculated in digitalized and interactively segmented nuclei using a differential box-counting method. The 3,575 nuclei studied showed a bimodal distribution (peaks at FD1 = 2.115 and FD2 = 2.180). The 75 percentile of the FD was an independent unfavorable prognostic factor for overall survival when tested together with ECOG (Eastern Cooperative Oncology Group) performance status, tumor extension, and therapy in a multivariate Cox regression. Our study corroborates the concept of two main chromatin configurations in small cell neuroendocrine carcinomas and that globally more open chromatin indicates a higher risk of metastasis and therefore a shorter survival of the patient.