DNA ploidy and morphology of colon tumors in the adenoma–carcinoma sequence

Abstract

Introduction. Chromosomal changes are widespread in the vast majority of colon carcinomas and aneuploidy is an established prognostic factor. However, this knowledge so far has no influence on tumor classification. We reported a morphology-based classification scheme, the core classification, that correlates with DNA ploidy. In particular, tripolar mitoses were identified as surrogate markers of a near triploid DNA content. In addition, a survey on chromosome numbers and survival rates in carcinomas suggested that triploidy as a particular state of aneuploidy may be correlated with a more aggressive tumor phenotype. We therefore aimed to analyse DNA ploidy in the colorectal adenoma-carcinoma sequence. Material and methods. The study collection consisted of 15 adenomas and 15 adenocarcinomas of 10 patients. Some of them showed a morphological transition between benign and malignant tumor components which were selectively analysed by DNA measurements. In addition, we assessed the morphological parameters of the core classification. Results. The main findings of the study may be summarized as follows. 1) DNA ploidy changes are already consistently detectable in colon adenomas. They are usually associated with hyperdiploidy. 2) Adenoma tissue adjacent to carcinomas, however, may carry a hypodiploid DNA content while the nearby carcinoma samples were hyperdiploid. Hypodiploidy may thus represent a transition state to near triploid carcinomas.3) The size of tumor nuclei and mitoses usually reflects the ploidy level of colon tumors. Specifically, triploid mitoses may point to a near triploid DNA content. 4) Triploidy per se cannot be equated with tumor aggressiveness as it may already be found in adenocarcinoma in situ. 5) Tripolar and tetrapolar mitoses in invasive colon cancer, however, are potential indicators of an advanced chromosomal instability and seemed to be associated with advanced tumor stages. Conclusions. We present data that hypodiploidy may represent a transition state from adenoma to carcinoma in a subset of colorectal tumors and that near-triploidy may be associated with a more aggressive course of the disease. However, the interpretation of tripolar mitoses and triploidy is largely dependent on the cell type (benign vs. malignant) and tissue context (invasive vs. non-invasive cancer). Furthermore, its interpretation may be distinct for different tumor stages and histotypes. Aneuploidy and multipolar mitoses are frequent findings in cancer cells. Their relevance for tumor biology deserves further studies.

KRAS and aneusomy of chromosomes 4, 10 and 12 in colorectal carcinomas

“…Furthermore, quantification of FISH signals has become a routine in predictive molecular pathology like HER2 analysis. In general, the frequency of aneuploid and near triploid cases of our FISH study is comparable with published DNA cytometry data [8,21,27]. In particular, our recent DNA ploidy analysis confirmed the presence of hypodiploid colon tumors and pointed to a putative relevance of hypodiploidy in the transition from adenomas to carcinomas [21].…”

“…In general, the frequency of aneuploid and near triploid cases of our FISH study is comparable with published DNA cytometry data [8,21,27]. In particular, our recent DNA ploidy analysis confirmed the presence of hypodiploid colon tumors and pointed to a putative relevance of hypodiploidy in the transition from adenomas to carcinomas [21]. We therefore feel that ploidy analysis by FISH together with the assessment of specific chromosomes with prognostic relevance may become a useful ancillary tool in tumor pathology.…”

“…The ploidy status of tumors is usually determined by DNA measurement using either flow cytometry or static DNA image analysis [8,21,27]. FISH represents an interesting alternative method because it is widely used in the diagnostic setup of many pathological institutes.…”

Colorectal cancers with a residual adenoma component: Clinicopathologic features and KRAS mutation

“…As the colorectal cancer grows in size, the adenoma portion may either disappear or remain a part of the tumor. A residual adenoma component in colorectal cancer has been noted due to the discordance of molecular test results in this component with that of an invasive component, but few reports have described the clinicopathologic features of colorectal cancers that include residual adenoma components [5][6][7][8][9][10]. Special subtypes of colorectal cancer with extremely well-differentiated (WD) histology, such as adenoma-like adenocarcinoma or villous adenocarcinoma, have also been reported; these lesions have distinctive clinical features and a better prognosis than conventional adenocarcinoma along with the possibility of being mistaken for an adenoma during biopsy [11][12][13].…”