Nonmucinous Colorectal Carcinomas Research Articles

Abstract PO-021: Humans cannot accurately detect mucinous colorectal carcinoma from CT images, can AI help?

Abstract Background: Mucinous colorectal carcinoma (CRC) is found in 10-20% of patients and is associated with worse prognosis and treatment resistance. The early identification of mucinous tumor component at baseline and monitoring resistant clones at follow-up is challenging in clinical practice, which hinders appropriate and timely treatment selection. At CT, being routinely acquired in clinical practice, mucinous tumors can be characterized by semantic features, such as hypoattenuation and more heterogeneous enhancement than the non-mucinous tumors (Wnorowski et al 2019). However, the diagnostic accuracy of such CT findings reaches at most 62% (Young et al 2007). This can be substantially improved by utilizing robust feature quantification using state-of-art machine learning and neural network techniques. Materials and Methods: 7 mucinous and 7 non-mucinous CRC CTs were included in the model development (80% training and 20% validation) and 2 mucinous and 2 non-mucinous independent patients were used to test the model performance. Multiple lesions (primary and metastatic) were semi-automatically segmented in 3D Slicer (N=32 development and N=12 test). Three different classification models were generated using CT images: (1) a logistic regression model based on a newly developed hypodense tissue connectivity (HTC) metric, (2) a logistic regression model using a set of automatically selected radiomics (RAD) features (shape, 1st order and 2nd order) and (3) a convolutional neural network model (CNN) based on the ResNet architecture and automatically selected features. HTC was computed as a ratio between the volume of the connected hypodense tissue (0<HU<30) and total tumor volume. CT images were converted to 2D axial sections to increase the input size for CNN (resulting in 952 images). Class weights were used to mitigate the effect of in-balance between the number of mucinous and non-mucinous images. Performance of the model was quantified with Accuracy (Acc), Sensitivity (Sen), Specificity (Spec) and AUC. Results: The classification performance of all three models was first assessed using 10-fold cross validation, where the RAD and CNN models performed better than HTC model. (Mean±std) RAD: Acc 0.9±0.15, Sen 0.92±0.15, Spec 0.9±0.2, AUC 0.95±0.13; CNN: Acc 0.93±0.05, Sen 0.93±0.03, Spec 0.93±0.19, AUC 0.95±0.01; HTC: Acc 0.72±0.23, Sen 0.7±0.4, Spec 0.75±0.33, AUC 0.84±0.32. However, the situation changed in test set, where HTC and CNN models provide the best results. RAD: Acc 0.67, Sen 1.0, Spec 0, AUC 0.5; CNN: Acc 0.97, Sen 0.98, Spec 0.96, AUC 0.97; HTC: Acc 0.92, Sen 1.0, Spec 0.75, AUC 1.0. Conclusions: All studied models improved the accuracy of mucinous lesion identification compared to the literature reported value. Further method development and validation on larger multi-center cohorts would allow gaining confidence in models applicability in the clinical setting. Citation Format: Kinga Bernatowicz, Raquel Perez Lopez, Hector Garcia Palmer, Elena Elez Fernandez, Jose Fernandez Navarro, Marta Ligero Hernandez, Alonso Garcia Ruiz, Manuel Escobar Amores. Humans cannot accurately detect mucinous colorectal carcinoma from CT images, can AI help? [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-021.

Role of ERCC1 expression in colorectal adenoma-carcinoma sequence and relation to other mismatch repair proteins expression, clinicopathological features and prognosis in mucinous and non-mucinous colorectal carcinoma.

There are several DNA repair pathways that protect cellular DNA from injury, such as nucleotide excision repair (NER) and mismatch repair (MMR). The protein product of the excision repair cross-complementation group 1 (ERCC1) gene plays a pivotal role in NER. The exact relationship between MMR proteins and ERCC1 is not well known in colorectal carcinoma (CRC). To investigate expression of ERCC1 and MMR proteins in colorectal mucinous carcinoma (MA) and non-mucinous carcinoma (NMA) using tissue microarray technique. We studied tumor tissue specimens from 150 patients with colorectal mucinous (MA) and non-mucinous adenocarcinoma (NMA). Tissue microarrays were constructed using modified mechanical pencil tips technique and immunohistochemistry for ERCC1, MLH1, MSH2, MSH6, and PMS2. NMA showed a significantly more frequent aberrant cytoplasmic expression than MA while MA showed a more frequent intact nuclear expression than NMA. There were no significant differences between the NMA and MA groups in the expression of MMR proteins. In NMA cases, ERCC1 expression was significantly related to MMR status while was not significantly related in MA cases. ERCC1 expression was not significantly related to overall and disease-free survival in both NMA and MA groups. this study is the first to investigate the relation between MMR status and ERCC1 expression in colorectal MA and NMA. ERCC1 expression was significantly related to MMR status only in NMA cases. Hence, the current study emphasizes that further research about the relation between various DNA repair pathways is needed.

Clinical and Histopathologic Features of Colorectal Adenocarcinoma in Crohn's Disease.

The aim of this study was to assess the histopathologic characteristics of colorectal carcinomas (CRC) in patients with Crohn's disease (CD). A higher frequency of microsatellite instability (MSI) is seen in mucinous compared with nonmucinous CRC which suggests that its pathogenesis involves distinct molecular pathways. Several publications reported a higher percentage of mucinous adenocarcinoma in CD patients with CRC. So far, there has been no investigation of MSI in CD patients with mucinous CRC. The medical records of patients who underwent surgery for CRC were reviewed and those with a history of CD identified. The data of histologic classification and MSI status of the tumor were investigated. Fourteen patients with CD-associated CRC were identified (5 female, 9 male) resulting in 20 CRC in total. Histologic investigation revealed 7 adenocarcinomas without a mucinous or signet ring cell component. All other CRCs harbored a mucinous (n=11) and/or signet ring cell (n=6) component. All tumors assessed for MSI were found to be microsatellite stable. Our data indicate that CRCs with signet ring cell and mucinous components were much more common in patients with CD than in patients with sporadic CRC. This observation suggests that CRC in CD represent an own entity with distinct histopathologic and molecular features. This may implicate potential consequences for diagnosis and therapy of CRC in CD in the future as well as new factors to identify patients with an increased risk for developing CRC in CD.

Aberrant Expression of Calretinin, D2-40 and Mesothelin in Mucinous and Non-Mucinous Colorectal Carcinomas and Relation to Clinicopathological Features and Prognosis.

CRC is a heterogeneous disease in terms of morphology, invasive behavior, metastatic capacity, and clinical outcome. Recently, many so-called mesothelial markers, including calretinin, D2-40, WT1, thrombomodulin, mesothelin, and others, have been certified. The aim of this study was to assess the immunohistochemical expression of calretinin and other mesothelial markers (D2-40 and mesothelin) in colorectal mucinous adenocarcinoma (MA) and non mucinous adenocarcinoma (NMA) specimens and relation to clinicopathological features and prognosis using manual tissue microarray technique. We studied tumor tissue specimens from 150 patients with colorectal MA and NMA who underwent radical surgery from January 2007 to January 2012. High-density manual tissue microarrays were constructed using a modified mechanical pencil tip technique, and paraffin sections were submitted for immunohistochemistry using Calretinin, D2-40 and mesothelin expressions. We found that NMA showed significantly more calretinin and D2-40 expression than MA In contrast, no statistically significant difference between NMA and MA was detected in mesothelin expression. There were no statistically significant relations between any of the clinicopathological or histological parameters and any of the three markers. In a univariate analysis, neither calretinin nor D2-40 expressions showed any significant relations to DFS or OS. However, mesothelin luminal expression was significantly associated with worse DFS. Multivariate Cox regression analysis proved that luminal mesothelin expression was an independent negative prognostic factor in NMA. In conclusion, Calretinin, D2-40 and mesothelin are aberrantly expressed in a proportion of CRC cases with more expression in NMA than MA. Aberrant expression of these mesothelial markers was not associated with clinicopathological or histological features of CRCs. Only mesothelin expression appears to be a strong predictor of adverse prognosis.

Aberrant expression of c-KIT and DOG-1 in mucinous and non-mucinous colorectal carcinomas and relation to clinicopathological features and prognosis

Aberrant expression of c-KIT and DOG-1 in mucinous and non-mucinous colorectal carcinomas and relation to clinicopathological features and prognosis

Aberrant expressions of c-KIT and DOG-1 in mucinous and nonmucinous colorectal carcinomas and relation to clinicopathologic features and prognosis.

c-KIT and DOG-1 are 2 highly expressed proteins in gastrointestinal stromal tumors. Few studies had investigated c-KIT, but not DOG-1, expression in colorectal carcinoma (CRC). This study aims to investigate expressions of c-KIT and DOG-1 in colorectal mucinous carcinoma and nonmucinous carcinoma using manual tissue microarray technique. In this work, we studied tumor tissue specimens from 150 patients with colorectal mucinous (MA) and nonmucinous adenocarcinoma (NMA). High-density manual tissue microarrays were constructed using modified mechanical pencil tip technique, and immunohistochemistry for c-KIT and DOG-1 was done. We found that aberrant c-KIT expression was detected in 12 cases (8%); 6 cases (4%) showed strong expression. Aberrant DOG-1 expression was detected in 15 cases (10%); among them, only 4 cases (2.7%) showed strong expression. Nonmucinous adenocarcinoma showed a significantly high expression of c-KIT, but not DOG-1, than MA. Aberrant c-KIT and DOG-1 expressions were significantly unrelated but were associated with excessive microscopic abscess formation. Neither c-KIT nor DOG-1 expression showed a significant impact on disease-free survival or overall survival. In conclusion, aberrant c-KIT and DOG-1 expressions in CRC are rare events, either in NMA or MA. Nonmucinous adenocarcinoma showed a significantly higher expression of c-KIT, but not DOG-1, than MA. The expressions of both in CRC are significantly unrelated but are associated with microscopic abscess formation. Neither c-KIT nor DOG-1 expression showed a significant impact on disease-free survival or overall survival. So, c-KIT and DOG-1 immunostaining is not a cost-effective method of identifying patients with CRC who may benefit from treatment with tyrosine kinase inhibitors.

Differential expression of matrix metalloproteinase-13 in mucinous and nonmucinous colorectal carcinomas

Colorectal carcinoma (CRC) is a major health problem all over the world. Mucinous CRCs are known to have a peculiar behavior and genetic derangements. This study aimed to investigate matrix metalloproteinase (MMP)-13 expression in mucinous and nonmucinous CRCs. We studied tumor tissue specimens from 150 patients with mucinous and nonmucinous CRC who underwent radical surgery from January 2007 to January 2012. High-density manual tissue microarrays were constructed using a modified mechanical pencil tip technique, and paraffin sections were submitted for immunohistochemistry using MMP-13. Statistical analysis was performed for clinical and pathological data of all studied cases together with MMP-13 expression in mucinous and nonmucinous groups. Mucinous carcinoma was significantly associated with young age, more depth of invasion, lymph node metastasis, and less peritumoral and intratumoral neutrophils. Nonmucinous carcinomas showed higher MMP-13 expression compared with mucinous carcinomas. Despite the negative or low expression of MMP-13, mucinous carcinomas had more depth of invasion and more frequency of lymph node metastasis than did nonmucinous carcinomas.

Loss of Galectin-3 Expression in Mucinous Colorectal Carcinomas is Associated With 5′CpG Island Methylation in Tunisian Patients

The β-galactoside-binding protein galectin-3 (gal-3) has pleitropic biological functions and has been implicated in cell growth, differentiation, adhesion, RNA processing, apoptosis, and malignant transformation. To investigate the pattern of inactivation of the gal-3 gene (LGALS3) in colorectal cancers (CRC), we studied a series of Tunisian patients with CRC to identify abnormal methylation in LGALS3 promoter using a methylation-specific PCR. We also examined the gal-3 gene expression by reverse transcription-PCR and the expression of gal-3 protein by immunohistochemistry. Analysis of DNA methylation in nonmucinous colorectal carcinomas expressing gal-3 protein showed an unmethylated profile of LGALS3 promoter, whereas gal-3 was aberrantly methylated in mucinous colorectal carcinomas. Complete loss of the gal-3 expression both at mRNA and the protein level was associated with the gal-3 methylation in the mucinous colorectal carcinomas. Our results show that methylation of the gal-3 promoter could be an important mechanism in the regulation of the expression of this gene in mucinous CRCs.

Genome-wide molecular characterization of mucinous colorectal adenocarcinoma using cDNA microarray analysis

Mucinous colorectal carcinoma exhibits distinct clinicopathological features compared to non-mucinous colorectal carcinoma. Previous studies have discovered several molecular genetic features in mucinous colorectal carcinomas, but have limitations as they are confined to a small number of molecules. To understand the mucinous colorectal carcinoma system, this study was designed to identify genes that are differentially expressed in mucinous colorectal carcinoma compared to non-mucinous colorectal carcinoma using cDNA microarrays. cDNA microarray experiments were performed using human cDNA 17k chips with 25 mucinous and 27 non-mucinous cancer tissues. Differentially expressed genes (DEGs) were determined by Welch's t-test and more accurate classifiers were selected from the DEGs using the prediction analysis for microarrays (PAM) software package. Array results were validated using quantitative real-time RT-PCR. The identified gene set was functionally investigated through in silico analysis. Sixty-two DEGs were identified and the 50 highest ranking genes could be used to accurately classify mucinous and non-mucinous colorectal carcinomas. The identified gene set included up-regulated TFF1 (4-fold), AGR2 (3.3-fold), FSCN1 (2.2-fold), CD44 (1.5-fold) and down-regulated SLC26A3 (0.2-fold) in MC. TFF1, AGR2 and SLC26A3 were validated by quantitative real-time RT-PCR. The functions of these DEGs were related to tumorigenesis (14 genes), cell cycle progression (6 genes), invasion (2 genes), anti-apoptosis (7 genes), cell adhesion and proliferation (5 genes) and carbohydrate metabolism (3 genes). We suggest that MC has distinct molecular characteristics from NMC and therefore, that the expression signatures of DEGs may improve the understanding of molecular pathogenesis and clinical behaviors in MC.

Genome-wide molecular characterization of mucinous colorectal adenocarcinoma.

e21042 Background: Mucinous colorectal carcinoma exhibits distinct clinicopathologic features compared to non-mucinous colorectal carcinoma. Previous studies have discovered several moleculargenetic features in mucinous colorectal carcinomas. Methods: To understand the systemic biology of mucinous colorectal carcinoma, this study was designed to identify differentially expressed genes (DEGs) in mucinous compared to nonmucinous colorectal carcinoma using cDNA 17k microarray chips in 25 mucinous and 27 non-mucinous cancer tissues. DEGs were determined by a Welch's t-test and more accurate classifiers were selected from DEGs via the Prediction Analysis for Microarray. Results: The identified gene set including upregulated TFF1 (4-fold), AGR2 (3.3- fold), FSCN1 (2.2-fold), CD44 (1.5-fold) and downregulated SLC26A3 (0.2-fold) in mucinous colorectal tissues was functionally investigated and genetic networks were generated. Sixty-two genes were determined and the 50 highest ranked genes of them could accurately classify mucinous and non- mucinous colorectal carcinomas. TFF1, AGR2, SLC26A3 were validated by quantitative real-time RT-PCR. The functions of these DEGs were related to tumorigenesis (14 genes), cell cycle progression (6 genes), invasion (2 genes), antiapoptosis (7 genes), cell adhesion and proliferation (5 genes) and carbohydrate metabolism (3 genes). The generated network also was associated with cancer invasion, mucin production and cell cycle progression. Conclusions: From the functional roles of these genes, we might suggest that expression signatures of the determined genes could contribute to invasiveness and poor prognosis of mucinous colorectal carcinoma and these gene set could provide better understanding of molecular pathogenesis. No significant financial relationships to disclose.

CT Differentiation of Mucinous and Nonmucinous Colorectal Carcinoma

The purpose of this study was to evaluate the CT findings that can help differentiate mucinous from nonmucinous colorectal carcinoma. CT scans of 86 patients with pathologically proven mucinous colorectal carcinoma were analyzed, and 105 consecutive patients with nonmucinous colorectal carcinoma were also included as a control group. CT findings were compared between the two groups with regard to the bowel involvement patterns; patterns of contrast enhancement; and presence or absence of bowel obstruction, intratumoral calcification, pericolic fat infiltration, and local tumor extension to adjacent organs. Statistical analyses were performed using the Student's t test and Pearson's chi-square test. Compared with nonmucinous carcinoma, mucinous carcinoma showed more severe (2.41 +/- 1.19 cm vs 1.94 +/- 0.92 cm) (p = 0.004) and more eccentric (22% vs 8%) (p = 0.025) bowel-wall thickening. Heterogeneous contrast enhancement was more common in mucinous than in nonmucinous carcinoma (83% vs 53%) (p = 0.001). Mucinous carcinoma showed more areas with hypoattenuation (p = 0.001), and the solid portion of mucinous carcinoma showed less enhancement than that of nonmucinous carcinoma (p = 0.001). Presence of intratumoral calcification was more frequent in mucinous carcinoma (21% vs 5%) (p = 0.001). Heterogeneous enhancement showed the highest sensitivity (82.6%) but moderate specificity (55.9%) in diagnosing mucinous carcinoma. Tumors with four or more CT findings with a statistically significant difference were mostly mucinous carcinoma, and the specificity was 87%. CT is useful in the differentiation of mucinous from nonmucinous colorectal carcinoma.

Relationship between MUC5AC and altered expression of MLH1 protein in mucinous and non-mucinous colorectal carcinomas

The main purpose of this study was to examine the expression of mucins and mismatch repair proteins in colorectal carcinomas. The immunohistochemical distribution of apomucins MUC2, MUC5AC, and the expression of MLH1 and MSH2 proteins were examined in 76 mucinous and 60 non-mucinous colorectal carcinomas. MUC2 was noted in all mucinous carcinomas, whereas MUC5AC was present in 41 cases only (54%). In non-mucinous carcinomas, MUC2 was expressed in 61.7% of the tumors; by contrast, MUC5AC was present in 20% of the cases. The expression level of apomucins was significantly different in mucinous and non-mucinous lesions ( p<0.001). Twenty-seven (35.5%) of the mucinous carcinomas showed no MLH1 expression, whereas 11 (18.3%) of the non-mucinous tumors did. This difference was statistically significant ( p<0.005). Altered expression of MSH2 protein was never observed. The lack of MLH1 expression was considerably more frequent in carcinomas with secretion of MUC5AC ( p<0.005). Our study has demonstrated this close relationship by immunohistochemical methods. In summary, our data show: (1) differences in the expression of mucins between mucinous and non-mucinous tumors; (2) a high frequency of altered MLH1 protein expression (35.5%) in mucinous carcinomas; (3) a significant relationship between the presence of MUC5AC and the altered expression of MLH1 protein in colorectal carcinomas.

Transcriptional Activation of the MUC2 Gene by p53

MUC2 is one of the major components of mucins that provide a protective barrier between epithelial surfaces and the gut lumen. We investigated possible alterations of MUC2 gene expression by p53 and p21(Sdi1/Waf1/Cip1) in a human colon cancer cell line, DLD-1, establishing subclones in which a tetracycline-regulatable promoter controls exogenous p53 and p21 expression. MUC2 mRNA more significantly increased in response to p53 than to p21. Unexpectedly, MUC2 expression was also induced in human osteosarcoma cells, U-2OS and Saos-2, by exogenous p53. We next performed a reporter assay to test the direct regulation of MUC2 gene expression by p53. Deletion and mutagenesis of the MUC2 promoter region showed that it contains two sites for transactivation by p53. Furthermore, an electrophoretic mobility shift assay indicated that p53 binds to those elements. We analyzed MUC2 expression in other cell types possessing a functional p53 after exposure to various forms of stress. In MCF7 breast cancer and A427 lung cancer cells, MUC2 expression was increased along with the endogenous p53 level by actinomycin D, UVC, and x-ray, but not in RERF-LC-MS lung cancer cells carrying a mutated p53. These results suggest that p53 directly activates the MUC2 gene in many cell types.

Regulation of the intestinal mucin MUC2 gene expression in vivo: evidence for the role of promoter methylation

In the present work we investigated the in vivo regulation of the mucin gene MUC2, which is overexpressed in all mucinous colorectal carcinomas. The inhibition of methylation by 5-azadeoxycytidine induces de novo expression of MUC2 in the colon carcinoma cell line COLO 205. The expression is retained in xenograft tissue and the cells give rise to MUC2-expressing tumours in nude mice. The strong expression of MUC2 in the normal human goblet cells and in the tissue of human mucinous colorectal carcinomas is associated with the average methylation of about 50% at every investigated CpG site of the MUC2 promoter. In contrast, MUC2 promoter in the non-expressing normal columnar cells and in the non-mucinous carcinoma tissue is methylated to nearly 100%. These data show that (i) low methylation of MUC2 promoter is associated with MUC2 expression in vivo and (ii) the pattern of MUC2 promoter methylation in the normal goblet or columnar cells most closely resembles that in mucinous or non-mucinous colorectal carcinomas, respectively. They indicate that MUC2 expression in vivo is regulated by promoter methylation and support the hypothesis that cells with goblet-like differentiation give rise to mucinous colonic carcinomas.

Prognostic significance of mucinous carcinoma of colon and rectum: a prospective case-control study.

The clinical meaning of mucinous type of colonic and rectal carcinoma is still controversial. We used clinicopathological and follow-up data prospectively recorded for our series of colon and rectum cancer to compare 2 matched groups of mucinous and nonmucinous cancer patients. Two-hundred-forty-eight patients operated for colon and rectum cancer between January 1986 and January 1997 were considered. Thirty-six patients showed mucinous pattern on histologic examination but only 29 (11.7%) had more than 50% of mucin-secreting acini and could be classified as mucinous type. The 29 mucinous cancer patients were compared with 212 nonmucinous cancer patients to evaluate differences in epidemiological and clinical features. A control group from the nonmucinous patients was sorted by matching for age, sex, location, and Dukes stage. In the case-control groups, survival was better for nonmucinous than for mucinous tumours. Many of the epidemiological findings already observed for mucinous carcinoma were also confirmed. The existence of prognostic, clinical, and epidemiological differences between mucinous and nonmucinous colorectal carcinoma, together with the preliminary reports about their difference as to genetic features, could support the hypothesis that mucinous type is a distinct biological entity.

Prognostic significance of mucinous carcinoma of colon and rectum: A prospective case-control study

Background and Objectives The clinical meaning of mucinous type of colonic and rectal carcinoma is still controversial. We used clinicopathological and follow-up data prospectively recorded for our series of colon and rectum cancer to compare 2 matched groups of mucinous and nonmucinous cancer patients. Methods Two-hundred-forty-eight patients operated for colon and rectum cancer between January 1986 and January 1997 were considered. Thirty-six patients showed mucinous pattern on histologic examination but only 29 (11.7%) had more than 50% of mucin-secreting acini and could be classified as mucinous type. The 29 mucinous cancer patients were compared with 212 nonmucinous cancer patients to evaluate differences in epidemiological and clinical features. A control group from the nonmucinous patients was sorted by matching for age, sex, location, and Dukes stage. Results In the case-control groups, survival was better for nonmucinous than for mucinous tumours. Many of the epidemiological findings already observed for mucinous carcinoma were also confirmed. Conclusions The existence of prognostic, clinical, and epidemiological differences between mucinous and nonmucinous colorectal carcinoma, together with the preliminary reports about their difference as to genetic features, could support the hypothesis that mucinous type is a distinct biological entity. J. Surg. Oncol. 2000;73:70–74. © 2000 Wiley-Liss, Inc.

Low frequency of p53 gene mutation and protein expression in mucinous colorectal carcinomas.

Immunohistochemical data indicate that the frequency of p53 protein overexpression is consistently lower in the mucinous than in the non-mucinous carcinomas of the breast, ovary, pancreas and colon. This peculiar immunohistochemical behavior of the mucinous phenotype could be due to the effect of large amounts of mucus on the staining or to an actual mutation frequency difference between mucinous and non-mucinous carcinomas. This question was investigated on a group of mucinous colorectal carcinomas. DNA was extracted from paraffin sections of 16 human mucinous colorectal carcinomas and the mutation frequency was determined by sequencing of p53 exons amplified in PCR. The expression of p53 protein was determined with the avidin-biotin complex-peroxidase staining procedure and CM-1 antiserum. Twenty-five percent of the tumors, exhibited p53 protein overexpression and in 31% a mutation was detected. Concordance between the two techniques was found in 69% of tumors. Overexpression without mutation was observed in 12% and mutation without overexpression in 19%. G:C --> A:T transitions represented the most frequent lesion (80%), as previously observed in non-mucinous colorectal carcinomas. These data indicate that the mutation pattern in the p53 gene is similar in mucinous and non-mucinous colorectal carcinomas. The low frequency of p53 overexpression in the mucinous phenotype is not due to a mucus effect on the staining but is related to the low mutation frequency of p53 gene. These results lead to the hypothesis that in contrast to the nonmucinous tumors the development of the majority of colonic carcinomas with the mucinous phenotype may be independent from p53 mutations.