Overlap of nuclear diameters in lung cancer cells

The nuclear diameters (NDs) of randomly selected malignant cells from 35 cases of small-cell lung cancer (SCLC; 4,370 nuclei) and 31 cases of non-SCLC (NSCLC; 1,280 nuclei) were measured on the pretreatment tissue sections by ocular micrometry. The mean ND (+/- standard deviation) of malignant cells for SCLC patients was 8.1 +/- 1.5 microns; these cases included 23 oat-cell carcinomas and 12 intermediate-cell carcinomas. The ND of malignant cells for NSCLC patients was 12.8 +/- 2.2 microns; these cases included 17 squamous-cell carcinomas, 12 adenocarcinomas and 2 large-cell carcinomas. The differences of ND between SCLC and NSCLC and between intermediate-cell cancer and NSCLC were highly significant (P = 0.001). However, the malignant cells of 36 (54.5%) of the 66 lung cancer patients had NDs that overlapped in the range of 8 microns to 13 microns. For the 12 intermediate-cell patients, the NDs of the malignant cells overlapped with those of 8 (66.7%) of the 12 adenocarcinomas and 10 (58.8%) of the 17 squamous carcinomas. In contrast, the NDs of only 5 (21.7%) of the oat-cell patients overlapped with those of 5 (41.7%) of the 12 intermediate-cell cases and showed no overlap with NSCLC cases. Since there is overlapping of the nuclear diameters of malignant cells between SCLC and NSCLC patients, nuclear parameters other than the diameter are necessary to differentiate these two major histologic types of lung cancers.     

Cytometric and histologic predictors of prognosis in ampullary carcinoma treated with pancreatico-duodenectomy

The association between several clinical, histologic and karyometric variables and the survival rates of patients with ampullary carcinoma was examined. Cases were limited to those treated exclusively by pancreaticoduodenectomy for which follow-up data was available, eliminating those cases with deaths due to other causes. The histologic type was classified as papillary, intestinal or mixed while the differentiation was recorded as well, moderate or poor. The stroma was categorized as scanty, moderate or abundant, and the tumor stage was evaluated according to Martin's classification. High-resolution morphometric and microphotometric (DNA content) evaluation of Feulgen-stained nuclei was performed using the microTICAS system. Statistical analyses were performed to examine the relationship between these variables and survival. Neither the tumor stage nor the presence of positive lymph nodes was a significant prognostic indicator, nor was the degree of differentiation or the amount of stroma. However, the survival showed a significant association with several karyometric variables and with the histologic type. Specifically, aneuploid DNA ploidy profiles, higher mean ploidy values and larger nuclei were associated with a lower survival rate. Short-term survivors (less than five years) had a mean ploidy of 2.8N, a mean 5N exceeding rate of 8.3% and a mean nuclear area of 41 sq microns, while long-term survivors (greater than or equal to five years) had corresponding means of 1.9N, 0.6% and 26 sq microns. These differences are all significant at a two-tailed significance level of less than .05 using a separate variance estimate t-test. In addition, papillary tumors showed a better prognosis than did intestinal or mixed tumors (Breslow P less than .04 and Mantel-Cox P less than .009).     

Nuclear volume and total optical density in Down syndrome

OBJECTIVE: To estimate nuclear size and integrated optical density of parenchymal cells from various organs in patients with Down syndrome and a control group. STUDY DESIGN: During the years 1988-2000, 14 cases of Down syndrome were found (8 male and 6 female). Ten infants without congenital anomalies died of respiratory distress syndrome and were used as a control group. Five nuclear variables were estimated: area, equivalent diameter, volume of equivalent sphere, roundness and total optical density (TOD). RESULTS: Mean nuclear volume and TOD of thyroid follicular cells were significantly lower in patients with Down syndrome (43.82 +/- 8.95 and 173.81 +/- 32.85 microns 3, respectively) than in the control group (65.46 +/- 15.31 and 234.58 +/- 32.85 microns 3, respectively) (P < .01). Mean hepatocite nuclear volume and TOD were significantly higher in the control group (165.54 +/- 55.42 and 220.84 +/- 51.75 microns 3, respectively) than in trisomy 21 (110.39 +/- 32.97 and 176.58 +/- 28.53 microns 3, respectively) (P < .05). CONCLUSION: The present results suggest altered gene expression in excessive genetic material, especially in thyroid follicular cells.     

Decreased matriptase/HAI-1 ratio in advanced colorectal adenocarcinoma of Chinese patients

Matriptase is a serine protease expressed by tumors of surface epithelial origin. We tested the expressions of matriptase and hepatocyte growth factor activator inhibitor-1 (HAI-1) maybe associated with the progression of colorectal adenocarcinoma. Immunohistochemical analysis of matriptase and HAI-1 was performed in tissue microarray slides of 91 colorectal adenocarcinomas with various degrees. The matriptase scores in moderately (346.7 +/- 10.6) and poorly differentiated (248.1 +/- 12.9) were significantly lower than those in well differentiated (368.4 +/- 9.6) colorectal adenocarcinomas. The matriptase/HAI-1 ratios in poorly (1.8 +/- 0.4) and moderately differentiated (1.8 +/- 0.3) were significantly lower than in well differentiated (2.2 +/- 0.2) colorectal adenocarcinomas. Otherwise, the matriptase scores and matriptase/HAI-1 ratio showed significant reverse correlation with more advanced TNM stages of colorectal adenocarcinomas in Chinese patients. In conclusion, pharmacological inhibitors of matriptase may not be effective treatment for advanced colorectal adenocarcinomas.     

Endocervical atypical glandular cells of undetermined significance. I. Morphometric and cytologic characterization of cases that "cannot rule out adenocarcinoma in situ"

OBJECTIVE: To determine whether evaluating morphologic features through morphometry and cytology can lead to a more-satisfactory characterization of endocervical atypical glandular cells of undetermined significance (AGUS) cases that "cannot rule out adenocarcinoma in situ" (AIS). STUDY DESIGN: Fifty-seven endocervical AGUS cases showing incomplete criteria of AIS were morphometrically compared to five smears with normal endocervical columnar cells (ECC) and to five histologically confirmed endocervical adenocarcinoma cases. For each atypical nucleus, the area and shape were measured. Twenty-five cytologic criteria were used to review the AGUS and neoplastic smears. RESULTS: AGUS nuclei showed an intermediate value in terms of area and shape as compared to the values of normal and neoplastic nuclei. In particular, AGUS nuclear enlargement (136.626 micron 2) was about twice the area of normal nuclei and half the value of the area of neoplastic nuclei (P < .0000). AGUS nuclei also had the greatest variability in size and shape, indicating that anisonucleosis may be a morphologic discriminator of endocervical AGUS. The cytologic features useful in discriminating AGUS from neoplastic smears were: presence of normal ECCs, singly or in sheets (P < .001); absence of necrosis (P < .001); bare atypical cells (P < .001); papillary groups (P < .01); anisonucleosis (P < .05); irregular chromatin distribution (P < .05); and hyperchromasia (P < .01). CONCLUSION: Morphometry and cytology led to a better characterization of endocervical AGUS cases that "cannot rule out AIS."     

Hereditary adenocarcinomatosis in 4 generations of a Valais family

An account is given of a family from the Canton of Valais, suffering from hereditary adenocarcinomatosis. The pedigree extends over four generations; the first three comprise 47 individuals (28 males, 19 females), of whom 21 (16 males and 5 females), i.e. 44.6%, are affected with malignant tumours. Of the 32 people in the fourth generation, only one individual is affected to date (a girl aged 21, IV/14). There were 27 tumours in all: 16 adenocarcinomas of the colon, two gastric adenocarcinomas, one duodenal adenocarcinoma, one rectal adenocarcinoma, one papillary carcinoma of the ovary, one osseous sarcoma, one cutaneous fibrosarcoma, a multiform glioblastoma of the basal nuclei of the brain, a basocellular epithelioma, also a cerebral metastasis from an adenocarcinoma, the origin of which has not been established, and a tumour invading the biliary tract. Three members of the family suffered from multiple tumours. In three of the patients, the colonic adenocarcinoma was accompanied by one or two polyps. The average age at the onset for all the tumours was 45 years. It was definitely lower in the third than the second generation (anticipation). The transmission was autosomal dominant, with predilection for the male sex (57.1% male and 26.3% female patients). The penetrance was about 80%. The author finally discusses the diagnostic criteria for hereditary adenocarcinoma and reviews the different familial forms of cancer.     

Ultrastructure of pleural mesothelioma and pulmonary adenocarcinoma in malignant effusions as compared with reactive mesothelial cells.

OBJECTIVE: To determine the ultrastructural features of diffuse malignant pleural mesothelioma cells in cytologic specimens from pleural effusions. STUDY DESIGN: We retrospectively studied 35 pleural effusions: 12 diffuse malignant pleural mesotheliomas (8 epithelial type, 4 biphasic type), 12 pulmonary adenocarcinomas and 11 cases of reactive mesothelial cells. RESULTS: In the cytoplasm, reactive and malignant mesothelial cells had more-abundant intermediate filaments (P < .05, P < .01) and fewer free ribosomes (P < .001, P < .001) than adenocarcinoma cells. Reactive mesothelial cells had fewer mitochondria than mesothelioma cells (P < .05). Mesothelioma cells had longer, thinner microvilli on the cell surfaces (P < .001); length/diameter ratios of microvilli were 19.1 +/- 7.0 (mesothelioma) vs. 9.1 +/- 2.2 (adenocarcinoma) and 9.2 +/- 2.4 (mesothelial cells). Giant intercellular junctions (desmosomes or desmosomelike structures > 1 micron in length) were found in eight cases of mesothelioma. Core filaments or rootlets in microvilli were present in two cases of adenocarcinoma. CONCLUSION: Because cytologic specimens from pleural effusions were easy to obtain, we think ultrastructural cytology is useful in distinguishing mesothelioma from adenocarcinoma and benign effusions.     

Implications of nuclear diameter in small cell lung carcinoma

The nuclear diameter of 5,117 malignant cells from 42 small cell lung carcinoma (SCLC) patients was assessed either on pretreatment tissue sections (35 cases) or cytologic smears (7 cases) by ocular micrometry. The SCLCs were subtyped as 30 oat cell carcinomas and 12 intermediate cell carcinomas according to the World Health Organization classification, based on the predominant histology of the tumor. The median number of nuclei measured from each patient was 110. All patients were treated identically by sequential hemibody and local irradiation combined with chemotherapy and had a median follow-up time of 310 days. The mean nuclear diameter (+/- standard error) obtained from tissue sections was 8.2 +/- 0.03 microns (median = 8.0), including 7.3 +/- 0.03 microns (median = 7.0) for oat cell cases and 9.5 +/- 0.06 microns (median = 9.0) for intermediate cell cases (P less than .001). In 28.6% of these patients, the nuclear diameter overlapped in the range of 8 microns to 9 microns between both subtypes. Comparisons between the nuclear diameter of primary and metastatic SCLC cells revealed no statistically significant differences. The nuclear diameter of malignant cells correlated with the mitotic index and stage of disease, but did not correlate with the other nuclear morphologic variables or with survival. The only identified prognostic factor was the stage of disease; these results indicate that the nuclear diameter of malignant cells should not be considered a prognosticator or a guide for therapy in SCLC patients.     

Cytologic characteristics of pulmonary papillary adenoma. A case report

BACKGROUND: Pulmonary papillary adenoma is a benign pulmonary neoplasm. Previously pulmonary papillary adenoma was described in terms of immunohistochemistry and ultrastructure. However, there are no previous reports describing the cytologic characteristics of pulmonary papillary adenoma. CASE: A 50-year-old male was admitted for evaluation of a coin lesion in the left upper lung field. Radiologic images showed a solid, round tumor approximately 25 mm in diameter in the left upper lung. Transbronchial needle aspiration biopsy (TBNA) was performed, and small numbers of atypical cells were collected. Adenocarcinoma was suggested clinically, and left upper segmentectomy was performed. The histologic diagnosis was pulmonary papillary adenoma. Imprint cytology of the cut surface of the tumor showed tumor cells arranged in sheets that contained scant or vesicular cytoplasm. The nuclei were oval or round, without obvious anisokaryosis, and their chromatin was fine, without hyperchromasia. Cytologically, the nuclei of the tumor cells in the imprint specimen (38.70 +/- 8.69 microns 2) were uniform in size and similar to the atypical cells in the TBNA specimen (38.29 +/- 11.56 microns 2) but significantly larger than the nuclei of the bronchial cells (23.61 +/- 5.98 microns 2) (P < .0001). CONCLUSION: The cytologic appearance of pulmonary papillary adenoma was characterized morphologically and morphometrically. The possibility of cytodiagnosis by TBNA was suggested.     

Haematogenous abdominal wall metastasis of differentiated, alpha-fetoprotein-negative hepatocellular carcinoma after previous antiandrogen therapy within a site of lipoma manifestation since childhood

Background

The guidelines established by the National Comprehensive Cancer Network do not describe mucinous histology as a clinical factor that should influence the therapeutic algorithm. However, previous studies show conflicting results regarding the prognosis of colorectal mucinous adenocarcinoma. In this study, we described the clinicopathological features of mucinous adenocarcinoma in Japan, to identify optimal therapeutic strategies.

Methods

144 patients with mucinous and 2673 with non-mucinous adenocarcinomas who underwent primary resection in two major centers in Yokohama, Japan were retrospectively evaluated for clinicopathological features and treatment factors. A multivariate analysis for overall survival followed by the comparison of overall survival using Cox proportional hazard model were performed.

Results

Patients with mucinous adenocarcinoma had larger primary lesions, higher preoperative CEA levels, a deeper depth of invasion, higher rates of nodal and distant metastasis, and more metastatic sites. A multivariate analysis for overall survival revealed a mucinous histology to be an independent prognostic factor. In the subgroup analysis stratified by stage, Patients diagnosed as StageIII and IV disease had a worse survival in mucinous adenocarcinoma than non-mucinous, while survival did not differ significantly in patients diagnosed as Stage0-II disease. In StageIII, local recurrence in rectal cases and peritoneal dissemination were more frequently observed in patients with a mucinous histology.

Conclusions

Our study indentified that mucinous adenocarcinoma was associated with a worse survival compared with non-mucinous in patients with StageIII and IV disease. In rectal StageIII disease with mucinous histology, additional therapy to control local recurrence followed by surgical resection may be a strategical alternative. Further molecular investigations considering genetic features of mucinous histology will lead to drug development and better management of peritoneal metastasis     

DNA flow cytometry of endoscopically examined colorectal adenomas and adenocarcinomas

DNA ploidy of 64 colorectal adenomas and 49 adenocarcinomas, examined endoscopically, was studied by flow cytometry. We found DNA aneuploidy in none of the 105 normal mucosa samples (0%), in 20 adenomas (31%), and in 36 adenocarcinomas (74%). DNA ploidy of adenomas correlated with size (P = 0.02) and degree of dysplasia (P less than 0.01) but not with histologic type. Adenomas had a 45% incidence of DNA aneuploid stem lines in the DNA index range of 0.80-1.20, compared with 8% in the case of adenocarcinomas. The distribution of the DNA index values of adenocarcinomas was approximately normal, with a mean value 1.63 +/- 0.28. The mean DNA index for the three cases of "carcinoma in adenoma" with invasion of the stalk of the adenoma was 1.52 +/- 0.18. These results, using DNA flow cytometry, provide evidence for the progression of colorectal adenoma to adenocarcinoma. The classification of adenomas according to DNA ploidy may be information of considerable practical value to the clinician in predicting risk of further adenomas and/or risk of cancer.     

Seminal vesicle epithelium as a potential pitfall in the cytodiagnosis of presacral masses. A report of two cases

BACKGROUND: Whenever abdominoperineal resection is performed because of a rectal adenocarcinoma, the prostate and seminal vesicles may be displaced backward to the presacral space, giving rise to a false radiologic image of a presacral tumor. Due to cytologic atypia associated with the epithelium of seminal vesicles, there is a real possibility, in fine needle aspiration biopsy (FNAB), of erroneously giving a malignant diagnosis. CASES: Two men, aged 53 and 57 years, presented with presacral masses three months and six years, respectively, after abdominoperineal resection for rectal adenocarcinoma. In both cases, FNAB smears showed some groups and single cells with large and irregular nuclei. These cells suggested a recurrence of carcinoma. The presence of cytoplasmic coarse pigment and a background with spermatozoa and blobs of inspissated secretory product were sufficient to determine that these presacral masses represented the seminal vesicles. CONCLUSION: Awareness that seminal vesicles may give rise to a radiologic impression of presacral tumor after abdominoperineal resection of the rectum will avoid unnecessary FNAB and a cytologic false positive diagnosis of colorectal adenocarcinoma.     

Quantitative ultrastructure of isolated Kupffer cells of rat liver

The average volume of isolated Kupffer cells of rat liver is 821 +/- 64 microns 3, the average surface being 423 +/- 24 microns 2 (599 microns 2, with cell processes included). The surface structure (pseudopodia, lamellipodia, filopodia, microvilli) of isolated cells is much less developed than that of Kupffer cells in situ. By morphometric characterization volume densities are 0.1264 +/- 0.0077 (SE) for mitochondria and 0.3591 +/- 0.0169 for lysosomal structures. The volume of mitochondria amount to 0.79 +/- 0.04 microns 3.     

Prognostic significance of DNA ploidy and morphometric analyses of adenocarcinoma of the uterine cervix

In an effort to improve the prognostic accuracy of the histologic criteria used for cervical adenocarcinomas, the nuclear DNA ploidy levels, means and standard deviations of nuclear areas and amounts of lumen and neoplastic tissue were quantitated. Useful thresholds in discriminating recurrent disease, as identified by logistic regression analysis, included a DNA ploidy level of 3.0 N, a percent of lumen of 34.6% and nuclear area mean and standard deviation of 53.1 sq micron and 20.1 sq micron, respectively. These parameters should provide useful guidelines in the visual assessment of histologic features that have prognostic significance.     

Macrophage size determinations in the diagnosis of tuberculous effusions

This study investigated the usefulness of macrophage size determinations in lymphocyte-rich pleural effusions to improve the cytologic diagnosis of tuberculous pleurisy. The size of pleural macrophages was analyzed by quantitative morphometric planimetry in 18 effusions due to tuberculosis, 21 effusions following radiotherapy for malignant disease and 10 effusions due to congestive heart failure. Macrophages were identified and clearly separated from mesothelial cells by latex phagocytosis and immunostaining with the monoclonal antibody My4 (CD14). The mean macrophage area (+/- standard deviation) in tuberculous effusions (92 +/- 14 sq micron) was significantly smaller than in postradiation (141 +/- 28 sq micron) and heart-failure effusions (154 +/- 22 sq micron) (P less than .0001). There was also a smaller ratio of mesothelial cells in tuberculous effusions (0.5 +/- 0.9%) in comparison with effusions following radiotherapy (4 +/- 5%) or congestive heart failure (10 +/- 12%). In summary, this study demonstrated some cytomorphologic parameters that may be helpful in the differential diagnosis of tuberculous effusions.     

Quantitative light and electron microscopic correlations of nuclear features in papillary thyroid and ovarian carcinomas

The light microscopic (LM) and electron microscopic (EM) features of nuclear bodies and nucleoli were quantitatively compared in ten papillary carcinomas each of thyroid (PC-Thy) and ovarian (PC-Ovar) origins, along with eight nonthyroid, nonovarian papillary neoplasms from other organs (PN-Oth). In each neoplasm, 100 randomly selected nuclei were scored for the presence of characteristic nuclear bodies; these were defined at the LM level by the presence of a central density surrounded by a clear halo, which corresponded to four distinct quantifiable images at the EM level. Means (+/- standard deviations) of the nucleolar frequency factor, the nucleolar area and the computed total nucleolar area (the product of the nuclear frequency factor and the mean nucleolar area) were assessed for the EM images. The number of nuclear bodies was 11.9 +/- 10.7 for PC-Thy, 5.2 +/- 5.3 for PC-Ovar and 5.9 +/- 7.4 for PN-Oth; the means for PC-Thy and PC-Ovar were significantly different (P less than .03), as were the means for PC-Thy and PN-Oth (P less than .04). The nucleolar frequency factor was 0.60 +/- 0.19 for PC-Thy, 1.19 +/- 0.51 for PC-Ovar and 0.99 +/- 0.22 for PN-Oth; these means were significantly different for PC-Thy versus PC-Ovar (P less than .01) and for PC-Thy versus PN-Oth (P less than .001). The mean nucleolar area was 1.19 +/- 0.45 for PC-Thy, 1.91 +/- 0.92 for PC-Ovar and 1.94 +/- 0.76 for PN-Oth; the means were significantly different for PC-Thy and PC-Ovar (P less than .05) and for PC-Thy and PN-Oth (P less than .05). The computed total nucleolar area was 0.73 +/- 0.41 for PC-Thy, 2.17 +/- 1.09 for PC-Ovar and 1.94 +/- 1.00 for PN-Oth; these means were significantly different for PC-Thy versus PC-Ovar (P less than .001) and for PC-Thy versus PN-Oth (P less than .01). A comparison of the total number of nuclear bodies, as determined by both LM and EM, indicated a significant correlation for the PC-Ovar (P less than .01) and PN-Oth (P less than .001) groups using linear regression analysis.(ABSTRACT TRUNCATED AT 400 WORDS)     

Comparison of different techniques for detection of Gal-GalNAc, an early marker of colonic neoplasia

The tumor marker, D-galactose-beta [1-3]-N-acetyl-D-galactosamine (Gal-GalNAc, also known as T-antigen) can be identified by a very simple galactose oxidase-Schiff's (GOS) reaction either on tissues or on rectal mucus samples from patients with colorectal neoplasms. Gal-GalNAc is expressed in the neoplastic mucosa as well as the remote non-neoplastic mucosa. It is, however, not expressed in colonic mucosa of normal subjects. We studied the expression of Gal-GalNAc by GOS reaction, lectin reactivity and immunocytochemistry in 10 normal, .45 precancerous [5 Crohn's disease, 15 ulcerative colitis (5 without dysplasia and 10 with dysplasia), 25 tubular adenomas], and 25 adenocarcinoma cases. Normal mucosa remote from tubular adenoma and adenocarcinoma was also studied. The GOS method was compared with reactivity of the lectin jacalin and immunostaining with antibody to T antigen (Anti-Tag Ab). GOS reaction was negative in all of the 10 normal specimens. Of the 5 Crohn's disease specimens, 2 were positive and 3 negative. In the 5 ulcerative colitis cases without dysplasia, positive reaction was seen in 2 cases and negative in 3. Of the 10 cases of ulcerative colitis with dysplasia, 5 showed positivity in dysplastic areas, and 3 of these were also positive in remote non dysplastic mucosa. Twenty of 25 tubular adenomas yielded a positive reaction in the adenoma, 14 of them showing positivity also in remote mucosa; 3 cases showed a positive reaction only in remote mucosa. Of the 25 adenocarcinomas, 21 showed a positive reaction in the adenocarcinoma as well as the remote mucosa. GOS reaction was intense in well differentiated adenocarcinoma and weak in poorly differentiated adenocarcinoma. Intense reaction was also seen in the intracellular mucus of some aberrant crypts and morphologically normal crypts remote from adenocarcinoma and tubular adenoma. GOS reaction showed an overall sensitivity of 75.7% and specificity of 100% for cancer and precancerous lesions. Jacalin reactivity was slightly more sensitive (84.3%) but less specific (80%) and Tag Ab reactivity even less sensitive (50%) but as specific (100%) for neoplastic and dysplastic mucosa. We conclude that the detection of the carbohydrate moiety Gal-GalNAc varies with the technique used. Compared to other techniques, GOS reaction is extremely simple and has a high degree of sensitivity and specificity. It can be used for detection of this tumor marker in remote non-neoplastic mucosa of patients with neoplasia or at risk of developing neoplasia. It, therefore, could be used as a cost effective screening test in rectal biopsy specimens of such patients.     

DNA/nuclear protein content in the evaluation of cell cycle modifications during colon carcinogenesis

OBJECTIVE: To investigate the colorectal adenomacarcinoma sequence by biparametric DNA/nuclear protein flow cytometry with the aim of evaluating cell cycle modifications during carcinogenesis. STUDY DESIGN: Paraffin-embedded specimens of 27 adenomas with mild/moderate dysplasia, 20 adenomas with severe dysplasia/intramucosal adenocarcinomas, 28 adenocarcinomas and 14 normal colon mucosa specimens were analyzed by biparametric DNA/nuclear protein content flow cytometric analysis in order to evaluate cell cycle modifications during colorectal carcinogenesis. RESULTS: The mean G0-G1A fraction of the cell cycle was 50.6% (SD +/- 17.2), 25.7% (SD +/- 15.1), 27.8% (SD +/- 11.7) and 29% (SD +/- 13.8) for normal mucosa, adenomas with mild/moderate dysplasia, adenomas with severe dysplasia and adenocarcinomas, respectively. The difference between normal mucosa and the other groups was statistically significant (P < .05), while no significant differences were detectable between adenomas with different degrees of dysplasia and adenocarcinomas. CONCLUSION: Our results show a decrease in G0-G1A in adenomas with mild/moderate dysplasia, suggesting that modification of the cell cycle may represent an early step in colon carcinogenesis, and they support the hypothesis that disregulation of cell cycle-controlling genes is an early event in the adenoma-carcinoma sequence.