Submucosal Invasive Colorectal Carcinoma Research Articles

Pathological risk factors for lymph node metastasis in patients with submucosal invasive colorectal carcinoma.

BackgroundRisk grade assessment determines therapy in patients with submucosal invasive colorectal carcinoma (CRC). However, treatment decisions are often difficult due to a lack of consensus on which risk factors should be considered. We aimed to identify predictive risk factors for lymph node metastasis (LNM) in a large cohort of submucosal invasive CRC patients from China.Patients and methodsFollowing collection of clinicopathological data and disease-free survival (DFS) rates from 290 patients who underwent radical intestinal resection with regional lymphadenectomy, we immunohistochemically assessed expression of DNA mismatch repair (MMR) proteins and p53. The correlation between clinicopathological parameters, MMR expression, p53 status, and LNM status was determined using chi-squared tests and logistic analysis. Receiver operator characteristic curve analysis was used to compare the predictive values. The DFS curves were plotted using the Kaplan–Meier method.ResultsLNM was detected in 15.5% of the cases (45/290 patients). Three pathological characteristics, high tumor differentiation grade, lymphovascular invasion (LVI), and tumor budding, were all positively related to LNM in univariate and multivariate analyses (P<0.05). MMR status did not correlate with either LNM or the pathological characteristics (P>0.05). Overexpression of p53 was associated with tumor budding status (P=0.036). With a negative predicative value of 0.92 and area under the curve of 0.76 (95% CI: 0.68–0.85), the combination of these three factors provided optimal predictive ability. Patients with all three risk factors had poorer DFS (P<0.001).ConclusionHigh tumor grade, LVI, and positive tumor budding serve as useful LNM predictors in submucosal invasive CRC.

Predictive Factors for Lymph Node Metastasis in Submucosal Invasive Colorectal Carcinoma: A New Proposal of Depth of Invasion for Radical Surgery.

Patients with lymph node metastasis (LNM) in submucosal invasive colorectal carcinoma (SM cancer) require additional surgical treatment after endoscopic dissection. However, because additional radical resection after endoscopic local resection may be unnecessary for cases without LNM, more specific criteria are required in order to diminish the incidence of further radical resection after endoscopic dissection. A total of 492 patients with biopsy-proven SM cancer who underwent curative surgery between January 2008 and December 2012 were collected and were divided into LNM group and no LNM group. The cutoff value for the depth of submucosal invasion was analyzed by a receiver operating characteristic (ROC) curve. In this retrospective study, the association between LNM and clinicopathologic factors was analyzed by logistic regression analysis. The depth of submucosal invasion of 1900μm was determined as the cutoff value by ROC curve. Significant, independent predictive factors for LNM included the depth of submucosal invasion>1900μm (odds ratio [OR] 7.5; 95% confidence interval [CI] 3.1-18.3; p<0.001), venous invasion (OR 2.4; 95% CI 1.1-5.5; p=0.03), and poorly differentiated/mucinous adenocarcinoma (OR 6.3; 95% CI 1.3-30.8; p=0.02). Our study demonstrates that the depth of submucosal invasion (>1900μm), vascular invasion and poorly differentiated/mucinous carcinoma were predictive factors of LNM in patients with SM cancer. These predictors may help to reduce the incidence of unnecessary surgery after endoscopic resection.

Novel predictors for lymph node metastasis in submucosal invasive colorectal carcinoma.

AIMTo evaluate a novel grading system to predict lymph node metastasis (LNM) in patients with submucosal invasive colorectal carcinoma (SICRC).METHODSWe analyzed the associations between LNM and various clinicopathological features in 252 patients with SICRC who had undergone radical surgery at the Seoul Saint Mary’s hospital between 2000 and 2015.RESULTSLNM was observed in 31 patients (12.3%). The depth and width of the submucosal invasion, lymphatic invasion, tumor budding, and the presence of poorly differentiated clusters (PDCs) were significantly associated with the incidence of LNM. Using multivariate analysis, the receiver operating characteristic curvewas calculated and the area under curve (AUC) was used to compare the ability of the different parameters to identify the risk of LNM. The most powerful clinicopathological parameter for predicting LNM was lymphatic invasion (difference AUC = 0.204), followed by the presence or absence of tumor budding (difference AUC = 0.190), presence of PDCs (difference AUC = 0.172) and tumor budding graded by the Ueno method (difference AUC = 0.128).CONCLUSIONOur results indicate that the tumor budding and the depth multiplied by the width measurements of submucosal invasion can provide important information for patients with SICRC.

Su1614 Predictive Endoscopic Findings of Positive Vertical Margin in Endoscopic Submucosal Dissection for Submucosal Invasive Colorectal Carcinoma: Towards Expanded Indications for Endoscopic Resection

Su1614 Predictive Endoscopic Findings of Positive Vertical Margin in Endoscopic Submucosal Dissection for Submucosal Invasive Colorectal Carcinoma: Towards Expanded Indications for Endoscopic Resection

Endoscopic features and management of diminutive colorectal submucosal invasive carcinoma.

The vast majority of diminutive (∼5 mm) colorectal tumors consist of a very low prevalence of advanced neoplasia, and a predict-resect-and-discard policy has been proposed recently in Western countries. The histology of some diminutive colorectal tumors reveals carcinoma, not adenoma, although the frequency is relatively low. Clarifying the endoscopic features of diminutive submucosal invasive colorectal carcinoma (CRC) during colonoscopy is important for managing diminutive lesions. A total of 111 cases of submucosal invasive CRC ≤ 10 mm were analyzed. The incidence of submucosal invasion in early CRC per gross type, size, location, pit pattern diagnosis, and rate of lymph node (LN) metastasis was evaluated. In diminutive tumors, the overall submucosal invasion rate in early CRC was 9.6%; however, depressed tumors had a significantly higher frequency of submucosal invasion than protruded or flat elevated tumors. There were no significant differences in the distribution of submucosal invasive CRC between the diminutive tumors and those that were 6-10 mm. The pit pattern diagnosis of diminutive submucosal invasive CRC was type VI pit pattern in all cases. Each case of submucosal invasive CRC was completely resected by en bloc endoscopic resection, and there were no cases of LN metastasis. Diminutive tumors with depression have a high frequency of submucosal invasive CRC and an initial indication for endoscopic resection.

Analysis of Predictive Factors for Lymph Node Metastasis in Submucosal Invasive Colorectal Carcinoma

Purpose: Submucosal invasive colorectal carcinoma (SICC) exhibits lymph node metastasis in about 10% of patients. Therefore, endoscopic resection is insufficient for cases of SICC at risk of lymph node metastasis, and surgical resection accompanied with lymph node dissection is necessary. However, because additional intestinal resection is unnecessary for cases without lymph node metastasis, more rigid criteria are required in order to decrease the incidence of unnecessary further intestinal resection. We retrospectively identified predictive factors for lymph node metastasis in submucosal invasive colorectal carcinoma. Methods: One hundred and two patients who underwent intestinal resection as the first treatment or additional intestinal resection after endoscopic resection at our department between 1999 and 2012 were enrolled in the present study. Clinicopathological factors were analyzed to determine predictive factors related to lymph node metastasis. Results: The multivariate analysis revealing only depth of submucosal invasion (≤2700 μm) was found to be a significant, independent predictive factor of lymph node metastasis (P = 0.04, Odds ratio: 4.18, 95% CI: 1.06 - 16.40). Conclusion: It is considered that the refinement of the criteria in the present study will be very useful, especially in the patients for whom careful judgment is required when considering additional intestinal resection.

Risk factors for vertical incomplete resection in endoscopic submucosal dissection as total excisional biopsy for submucosal invasive colorectal carcinoma

Endoscopic submucosal dissection (ESD) for colorectal tumor is a minimally invasive treatment. Histologic information obtained from the entire ESD specimen is important for therapy selection in submucosal invasive colorectal carcinoma (SMca). This study aimed to identify risk factors for vertical incomplete resection (vertical margin-positive [VM+]) when ESD was performed as total excisional biopsy for SMca. From June 2003 through December 2011, 78 SMca cases were resected by ESD at Hiroshima University Hospital. Patient and tumor characteristics, intraoperative variables, and histopathology were compared between the VM+ group and the vertical complete resection (vertical margin-negative) group. The ability of magnifying endoscopy (ME) and endoscopic ultrasonography (EUS) to predict VM+ was assessed. ESD resulted in VM+ in eight cases (10.3%), with a greater percentage invading to a depth of ≥2,000 vs. <2,000μm (P = 0.047). Severe submucosal fibrosis was found in five of the eight cases (62.5%, P = 0.017). Poor differentiation was seen at the deepest invasive portion in six cases (75.0%), and two of six cases had an invasion depth <2,000μm. Of 39 EUS cases, 36 not showing deep invasion close to the muscularis propria were completely resected by ESD. Submucosal fibrosis and poor differentiation at the deepest invasive portion may be risk factors for VM+ in colorectal ESD for tumors with submucosal deep invasion. ME plus EUS is more likely to help determine whether ESD is indicated as complete total excisional biopsy for SMca.

Risk analysis of submucosal invasive rectal carcinomas for lymph node metastasis to expand indication criteria for endoscopic resection

In the 2010 guidelines for the treatment of colorectal cancer from the Japanese Society for Cancer of the Colon and Rectum (JSCCR), the criteria for identifying curable submucosal invasive colorectal carcinoma after endoscopic resection is as follows: differentiated adenocarcinoma, no vascular invasion, submucosal invasion depth <1000 μm and budding grade 1 (low grade). A total of 118 rectal submucosal carcinomas, treated by primary surgical resection or additional surgical resection with lymph node (LN) dissection, were analyzed. Relationships between clinicopathological findings and LN metastasis were evaluated. LN metastasis was found in 11.0% (13/118). There were no significant differences between clinicopathological findings and LN metastasis except for budding grade. Multivariate logistic regression analysis showed budding grade 2/3 (high grade) to be the independent risk factor for LN metastasis. When cases that met the curative condition of histological grade, tumor budding grade and vessel invasion together according to JSCCR 2010 criteria, the incidence of LN metastasis was only 2.2% (1/46, 95% confidence interval: 0.06-11.5%), regardless of the degree of submucosal invasion depth. In conclusion, even in cases of rectal carcinoma with submucosal deep invasion, the risk of LN metastasis is minimal under certain conditions.

Prognostic and Diagnostic Significance of Tumor Budding Associated with β-Catenin Expression in Submucosal Invasive Colorectal Carcinoma

Endoscopic resection has become a major curative treatment for early colorectal carcinoma without lymph node metastasis. However, lymph node metastasis, a poor prognostic factor in colorectal carcinoma, occurs in about 10% of the patients with submucosal invasive colorectal carcinoma. Therefore, it is important to identify a high-risk factor for lymph node metastasis in submucosal invasive colorectal carcinoma. This study was designed to identify the relationship between tumor budding with β-catenin expression and lymph node metastasis in submucosal invasive colorectal carcinoma. We investigated the immunohistochemistry of tumor budding in the 142 patients who underwent surgical resection for submucosal invasive colorectal carcinomas between 1984 and 1999 and the expression pattern of β-catenin in budding tumor cells. Accordingly, all the patients were followed up for at least 10 years or until death. Among the 142 patients, lymph node metastasis was detected in 14 patients (9.9%). Univariate analysis showed that tumor budding with ≥ 5 tumor cells or cell clusters with expression of β-catenin in the nucleus was significantly associated with lymph node metastasis (P = 0.005). In contrast, tumor budding detected by hematoxylin and eosin staining was not associated with lymph node metastasis. Multivariate logistic regression analysis showed that tumor budding with ≥ 5 tumor cells or cell clusters with expression of β-catenin in the nucleus was a significant risk factor for lymph node metastasis (odds ratio, 7.124; 95% confidence interval, 1.407-36.062). Thus, tumor budding associated with β-catenin expression is a risk factor for lymph node metastasis in submucosal invasive colorectal carcinoma.

Tumor budding as a risk factor of lymph node metastasis in submucosal invasive T1 colorectal carcinoma: a retrospective study

BackgroundThis study was designed to identify risk factors for lymph node metastasis of early stage colorectal cancer, which was confirmed to a carcinoma that invaded the submucosa after radical resection.MethodsIn total, 55 patients revealing submucosal invasive colorectal carcinoma on pathology who underwent curative radical resection at the Department of Surgery, St. Vincent’s Hospital, The Catholic University of Korea from January 2007 to September 2010 were evaluated retrospectively. Tumor size, depth of submucosal invasion, histologic grade, lymphovascular invasion, tumor budding, and microacinar structure were reviewed by a single pathologist. Student t-test for continuous variables and Chi-square test for categorical variables were used for comparing the clinicopathological features between two groups (whether lymph node involvement existed or not). Continuous variables are expressed as the mean ± standard error while statistical significance is accepted at P < 0.05.ResultsThe mean age of 55 patients (34 males and 21 females) was 61.2 ± 9.6 years (range, 43–83). Histologically, eight (14.5%) patients had metastatic lymph node. In the univariate analysis, tumor budding (P = 0.047) was the only factor that was significantly associated with lymph node metastasis. Also, the tumor budding had a sensitivity of 83.3%, a specificity of 60.5%, and a negative predictive value of 0.958 for lymph node metastasis in submucosal invasive T1 colorectal cancer.ConclusionsThe tumor budding seems to have a high sensitivity (83.3%), acceptable specificity (60.5%), and a high negative predictive value (0.958). A close examination of pathologic finding including tumor budding should be performed in order to manage early CRC properly.

Pathological prognostic factors predicting lymph node metastasis in submucosal invasive (T1) colorectal carcinoma

Lymph node metastasis occurs in as many as 16% of patients with submucosal invasive colorectal carcinoma. We investigated the association between histopathological factors and lymph node metastases in 322 consecutive patients with submucosal invasive colorectal carcinoma who had undergone radical colectomy with lymph node dissection to detect patients at high risk of lymph node metastasis without measuring the depth of submucosal invasion. Lymph node metastasis was found in 46 (14.3%) of 322 patients with submucosal invasive colorectal carcinoma. Univariate analysis showed that each of the following histopathological factors had a significant influence on lymph node metastasis: invasion depth, lymphatic invasion, venous invasion, tumor differentiation, growth pattern of the intramucosal tumor component, complete disruption of the muscularis mucosa due to tumor invasion, and tumor budding at the submucosal invasive front. Multivariate analysis showed that lymphatic invasion (P<0.01), tumor differentiation (P<0.01), and tumor budding (P<0.01) were significantly associated with lymph node metastasis. All 46 cases of lymph node metastasis showed at least one of the following findings: lymphatic invasion, moderately or poorly differentiated tumor grade, tumor budding, or complete disruption of the muscularis mucosa due to tumor invasion. Patients with submucosal invasive colorectal carcinoma that show at least one of three factors—lymphatic invasion, moderately or poorly differentiated tumor grade, or tumor budding—are at high risk for lymph node metastasis. All of the patients with lymph node metastasis, who did not have any of these factors, showed a completely disrupted muscularis mucosa.

Risk Factors for Lymph Node Metastasis in Patients with Submucosal Invasive Colorectal Carcinoma

Purpose: This study was designed to determine the risk factors of lymph node (LN) metastasis in patients with submucosal invasive colorectal cancer (SICC). Methods: Between January 1998 and January 2009, we reviewed patients who had undergone radical colon resection with LN dissection for SICC. Results: There were 36 males and 40 females (mean age, 61.1 years; range, 35∼86 years). In the univariate analysis, the risk of LN metastasis was related to the depth (absolute and relative), lymphovascular invasion, tumor budding, and tumor differentiation (P＜0.05). The relative depth by Kudo classification and lymphovascular invasion were significant predictors of LN metastasis both in univariate and multivariate analysis. In SICC with an absolute depth ＜1,800㎛, no LN metastasis was detected. Regardless of the size of the SICC, tumors that invaded within the sm2 layer and had no lymphovascular invasion had no LN metastasis. Conclusion: In the SICC, lymphovascular invasion and depth of submucosal invasion are strong predictors of LN metastasis. If deep invasion exceeds sm2 and positive lymphovascular invasion exists in the resected specimen, additional colectomy with LN dissection appears to be necessary.

Prolongation of the period between biopsy and EMR can influence the nonlifting sign in endoscopically resectable colorectal cancers

The nonlifting sign is widely used for evaluating the invasion depth of colorectal tumors, and it is commonly accepted that EMR is contraindicated for colorectal tumors with a nonlifting sign because of the probability of massive submucosal invasion. To identify the clinicopathologic factors that affect the nonlifting sign in submucosal invasive colorectal carcinoma (SICC). Details regarding a history of biopsy, postbiopsy days, tumor location, tumor configuration, tumor size, depth of submucosal invasion, histologic type, adenomatous remnants, and angiolymphatic invasion were studied in relation to the nonlifting sign. National Cancer Center, Korea. The study involved 76 patients with SICC treated by endoscopic or surgical resection, in whom the tumor was examined for the nonlifting sign from 2001 to 2006. The nonlifting sign was observed in 15 cases (19.7%). A deep submucosal invasion, a history of biopsy, and the absence of adenomatous remnants were identified as factors affecting the nonlifting sign in univariate and multivariate analyses (P < .05). An increase in the number of postbiopsy days was associated with the nonlifting sign in endoscopically resectable SICC, and all 11 sm1 cancer cases with fewer than 21 postbiopsy days showed lifting. A history of biopsy and the absence of adenomatous remnants, in addition to deep submucosal invasion, were found to influence the nonlifting sign in SICC. It may be best that mechanical stimulation such as forceps biopsies are minimized before EMR, and EMR should be tried as soon as possible if biopsy was performed.

Histopathological and genetic differences between polypoid and non-polypoid submucosal colorectal carcinoma

To investigate the histopathological and genetic differences between polypoid growth (PG) and non-polypoid growth (NPG) submucosal invasive colorectal carcinoma (CRC). A total of 96 cases of submucosal CRC were divided into two groups according to their growth type; 60 cases of PG and 36 cases of NPG. The size, histological degree of dysplasia, depth of submucosal invasion and lymph node metastasis were compared between the two groups. Furthermore, expression of p53 was detected by immunohistochemical staining, and K-ras gene mutation was examined by polymerase chain reaction based single-strand conformation polymorphism (SSCP). The average size of the lesions in the NPG group was significantly smaller than those in the PG group (7.5 mm vs 13.8 mm, P<0.001). The histological degree of dysplasia tended to be more severe in NPG group, while the incidence of submucosal massive invasion and the lymph node metastasis were both significantly higher in the NPG type than in the PG group (64.3% vs 43.3%, P=0.004; 43% vs 7%, P=0.008, respectively). In addition, K-ras gene mutations were detected in 67% of lesions in the PG group, but none in the NPG group, while no difference in p53 immunohistochemical expression was found between the two groups. Compared with PG submucosal CRC, NPG type demonstrates more frequent submucosal massive invasion, more lymph node metastasis and a higher degree dysplasia. Genetically, NPG type shows much less frequent K-ras mutation.

Histopathological risk factors for lymph node metastasis in submucosal invasive colorectal carcinoma of pedunculated or semipedunculated type

Aims: To evaluate the histopathological risk factors for lymph node metastasis in cases of pedunculated or semipedunculated submucosal invasive colorectal carcinoma (SICC). Methods: A total of 48 patients with non-sessile...

Evaluation of Tumor Cell Dissociation as a Predictive Marker of Lymph Node Metastasis in Submucosal Invasive Colorectal Carcinoma

Tumor cell dissociation-the histologic finding of small solid carcinoma cell clusters and groups of dissociated dedifferentiated carcinoma cells at the invasive front-is related to tumor metastasis and patient prognosis. However, few previous reports have examined tumor cell dissociation in submucosal invasive colorectal carcinoma. We investigated the relation between tumor cell dissociation and lymph node metastasis in submucosal invasive colorectal carcinoma. We also examined immunohistochemical expression of E-cadherin and beta-catenin in submucosal invasive colorectal carcinoma. Submucosal invasive colorectal carcinoma tissue samples from 20 patients with lymph node metastasis and 100 patients without lymph node metastasis were evaluated. Sections stained with hematoxylin and eosin were evaluated for tumor cell dissociation. Immunohistochemistry was used to determine the expression and cellular distribution of E-cadherin and beta-catenin. Tumor cell dissociation was more frequently identified in submucosal invasive colorectal carcinoma cases with lymph node metastasis than in those without lymph node metastasis (P = 0.0001). Decreased membranous expression of E-cadherin occurred more frequently in submucosal invasive colorectal carcinoma cases with lymph node metastasis than in those without lymph node metastasis (P = 0.025). Nuclear expression of beta-catenin tended to be present in submucosal invasive colorectal carcinoma cases with lymph node metastasis (P = 0.063). Decreased membranous expression of E-cadherin occurred more frequently in submucosal invasive colorectal carcinoma cases with tumor cell dissociation than in those without tumor cell dissociation (P = 0.0023). Our results suggest that there is a relation between tumor cell dissociation and lymph node metastasis in submucosal invasive colorectal carcinoma. Tumor cell dissociation formation might be related to abnormal expression patterns of E-cadherin and beta-catenin in submucosal invasive colorectal carcinoma. Tumor cell dissociation and decreased membranous expression of E-cadherin would be important predictive markers for lymph node metastasis in submucosal invasive colorectal carcinoma.

Predictive Histopathologic Factors for Lymph Node Metastasis in Patients With Nonpedunculated Submucosal Invasive Colorectal Carcinoma

Risk factors for lymph node metastasis in patients with nonpedunculated submucosal invasive colorectal carcinoma remain to be characterized. This study examines the relationship between lymph node metastasis and clinicopathologic factors in nonpedunculated submucosal invasive colorectal carcinoma. The study cohort comprised 155 patients who had undergone surgical treatment for nonpedunculated submucosal invasive colorectal carcinoma. The clinicopathologic factors investigated included gender, age, tumor location, macroscopic type, tumor size, histologic type and grade, intramucosal growth pattern, lymphatic invasion, venous invasion, degree of focal dedifferentiation at the submucosal invasive front, status of the remaining muscularis mucosa, and the depth and width of submucosal invasion. Lymph node metastases were found in 19 patients (12.3 percent). Univariate analysis showed that lymphatic invasion, focal dedifferentiation at the submucosal invasive front, status of the remaining muscularis mucosa, and depth of submucosal invasion all had a significant influence on lymph node metastasis. Multivariate analysis showed lymphatic invasion (P = 0.014) and high-grade focal dedifferentiation at the submucosal invasive front (P = 0.049) to be independent factors predicting lymph node metastasis. No lymph node metastasis was found in tumors with a depth of submucosal invasion of <1.3 mm. Lymphatic invasion and high-grade focal dedifferentiation at the submucosal invasive front are important predictors of lymph node metastasis in patients with nonpedunculated submucosal invasive colorectal carcinoma. Depth of submucosal invasion can be used as an identifying marker for patients who do not require subsequent surgery after endoscopic resection.

Correlations between lymph node metastasis and depth of submucosal invasion in submucosal invasive colorectal carcinoma: a Japanese collaborative study.

Depth of submucosal invasion (SM depth) in submucosal invasive colorectal carcinoma (SICC) is considered an important predictive factor for lymph node metastasis. However, no nationwide reports have clarified the relationship between SM depth and rate of lymph node metastasis. Our aim was to investigate the correlations between lymph node metastasis and SM depth in SICC. SM depth was measured for 865 SICCs that were surgically resected at six institutions throughout Japan. For pedunculated SICC, the level 2 line according to Haggitt's classification was used as baseline and the SM depth was measured from this baseline to the deepest portion in the submucosa. When the deepest portion of invasion was limited to above the baseline, the case was defined as a head invasion. For nonpedunculated SICC, when the muscularis mucosae could be identified, the muscularis mucosae was used as baseline and the vertical distance from this line to the deepest portion of invasion represented SM depth. When the muscularis mucosae could not be identified due to carcinomatous invasion, the superficial aspect of the SICC was used as baseline, and the vertical distance from this line to the deepest portion was determined. For pedunculated SICC, rate of lymph node metastasis was 0% in head invasion cases and stalk invasion cases with SM depth <3000 micro m if lymphatic invasion was negative. For nonpedunculated SICC, rate of lymph node metastasis was also 0% if SM depth was <1000 micro m. These results clarified rates of lymph node metastasis in SICC according to SM depth, and may contribute to defining therapeutic strategies for SICC.

Loss of standard type of CD44 expression in invaded area as a good indicator of lymph-node metastasis in colorectal carcinoma.

Recent advances have made possible the treatment of small invasive colorectal cancer by means of polypectomy or endoscopic mucosal resection. CD44 expression in cancer cells was identified as an indicator of lymph-node metastasis, which could be evaluated in specimens removed by colonoscopy. The correlation between lymph-node metastasis and the expression of standard-type CD44 in cancer cells was examined immunohistologically using the invaded cancer cells of 61 tissue samples of superficially invasive colorectal cancer. We defined the above as invasive cancer restricted within the colorectal wall. Of the 61 samples, 31 had submucosal invasion and 30 had muscular invasion. Standard-type CD44 expression in the area of invasion in cases with lymph-node metastasis was remarkably down-regulated. In 43 cases with no lymph-node metastasis, 36 (83.7 percent) of patients had CD44 expression in invaded cells, whereas only two of 18 cases (11.1 percent) with lymph-node metastasis had expression of standard-type CD44 in the same area (P < 0.0001). A total of 69.6 percent (16/23) of patients with loss of standard-type CD44 expression in invaded sites were found to have positive metastasis in the lymph nodes. These results suggest that standard-type CD44 in invasive colon cancer cells could suppress metastasis to the regional lymph nodes. In cases of invasive colorectal cancer, the loss of standard-type CD44 expression in the invaded area is a sensitive marker for metastasis to the lymph nodes. Further investigation with larger patient groups is required to clarify the reliability of loss of standard-type CD44 expression as an indicator for additional surgery after endoscopic resection of submucosal invasive colorectal carcinoma.

Proliferating cell nuclear antigen and p53 protein expression in submucosal invasive colorectal carcinoma.

In some cases of early colorectal carcinoma, radical surgical resection might be required because of vessel invasion, distant metastasis, or inadequate surgical margin. To characterize submucosal invasive colorectal carcinoma, we investigated expression of PCNA and p53 protein. Sixty-seven patients who underwent curative resection of submucosal invasive colorectal carcinoma participated in this study. The PCNA labeling index (PCNA-LI) is determined at the deepest lesion of carcinoma. The expression of PCNA and p53 protein were analyzed according to clinicopathological factors. 1) The PCNA-LI was correlated to histological grade, depth of invasion or vessel invasion in polypoid type. 2) The flat type had significantly higher PCNA-LI (65.1+/-8.2%) and p53 protein expression (69.6%) than the polypoid type. 3) The PCNA-LI was higher in cases with lymph node metastasis than in these without lymph node metastasis. 4) Overexpression of the p53 protein was detected in all cases with liver metastasis. Our results suggest that in order to determine the treatment for the patients with submucosal invasive colorectal carcinoma, the expression of PCNA and p53 protein may be a useful biologic marker.