Abstract

Malignancy associated changes (MAC) can be defined as subtle morphological and physiologic changes that are found in ostensibly normal cells of patients harboring malignant disease. It has been postulated that MAC have a potential to become a useful tool in detection, diagnosis and prognosis of malignant diseases. An in vitro cell culture model system was designed to study interactions between non‐small cell lung cancer (NSCLC) and the normal bronchial epithelium of the human respiratory tract in vivo to see if the MAC‐like phenomenon can be detected in such a system. In this study we examined changes in nuclear features of normal human bronchial epithelial cells (NHBE) when they were co‐cultured with cells derived from a lung cancer cell line NCI‐H460. Using discriminant function analysis, nuclear features were determined which allow maximal discrimination between normal cells incubated with or without cancerous cells. Our results demonstrate that MAC appear to be specific to changes induced by malignancy, and that these changes differ from those induced by growth factors in the serum. This study provides evidence in support to the hypothesis that MAC are induced by a soluble factor(s) released by malignant cells. Colour figure can be viewed on http://www.esacp.org/acp/2003/25‐2/sun.htm.

Highlights

  • Malignancy associated changes (MAC) are defined as subtle morphological and physiologic changes that are found in normal cells of patients harboring malignant disease

  • A large number of nuclear features showed significant differences in mean values and variances when group of normal human bronchial epithelial cells (NHBE) cells co-cultured with the highest concentration of NCI-H460 cells was compared with NHBE cells incubated with controls

  • Fractal measure of imaginary 3-dimensional surface created by the optical density function of the nucleus; gives highest values for nuclei with frequent and significant changes of optical density

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Summary

Introduction

Malignancy associated changes (MAC) are defined as subtle morphological and physiologic changes that are found in normal cells of patients harboring malignant disease. These changes were first observed by Gruner in 1916 [10], while the term “MAC” was first described by Nieburgs in the late 1950s in buccal mucosa [20]. In both cases, these changes were found in patients with late stages of malignancy. Thereafter many other laboratories reported the measurements of MAC by a variety of nuclear and cellular features, all of which were consistent with subtle changes in morphology of the normal cells growing in the vicinity of a malignant growth

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