Expression of the Cancer Stem Cell Markers CD44 and CD133 in Colorectal Cancer: An Immunohistochemical Staining Analysis

PURPOSE: The aim of this study was to assess the expressions of CD44 and CD133 in colorectal cancer tissue by using immunohistochemical staining and to analyze the clinical significance of the expressions related to other clinicopathological data and survival results. METHODS: One hundred sixty-two patients with a biopsy-proven colorectal adenocarcinoma who were operated on between January 1998 and August 2004 were enrolled in this study. Immunohistochemical staining for CD44 and CD133 was performed on primary colorectal cancer tissue, metastatic lymph nodes, and synchronous and metachronous metastatic tumor tissues if available. RESULTS: CD44 expression was stronger in the primary tumor than in metastatic lymph nodes (P < 0.001), and CD133 expression tended to be stronger in primary tumor than in metastatic lymph nodes (P = 0.057). No significant correlation was found between the CD44 and the CD133 expressions. The cases with recurrence showed low expression of CD44 (P = 0.017). CD133 expression was lower in cases with elevated CA 19-9 serum levels (P = 0.028) and advanced T stage (P = 0.038). Multivariate analysis proved that low expression of CD44 was an independent prognosis factor for short disease-free survival (P = 0.028). CONCLUSION: Low CD44 expression was correlated with increased tumor recurrence and short disease-free survival, and low CD133 expression was associated with advanced tumor stage. We suggest that further studies be performed to evaluate whether the immunohistochemical method for determining the CD44 and the CD133 expressions is appropriate for exploring cancer stem-cell biology in patients with colorectal cancer.

Inflammation-based score (Glasgow prognostic score) as an independent prognostic factor in colorectal cancer patients

PURPOSE: This study was conducted to evaluate the systemic inflammatory response in colorectal cancer patients, and to estimate the usefulness of the Glasgow prognostic score (GPS) as a prognostic factor. METHODS: Patients with biopsy-proven colorectal adenocarcinoma who were operated between April 2005 and December 2008 were enrolled in this study. The GPS was estimated based on the measurement of CRP and serum albumin level. The GPS was compared with other clinicopathological factors. Univariate and multivariate analyses were performed to evaluate the factors affecting cancer-specific survival. RESULTS: GPS was significantly higher in patients with anemia, thrombocytosis, a high neutrophil to lymphocyte ratio, tumor of the colon, and large tumor. Patient age, gender, serum CEA level, tumor gross appearance, TNM stage, and tumor differentiation were not related with the GPS. In univariate analysis, hemoglobin, CEA, gross appearance of tumor, TNM stage, tumor differentiation, and GPS were associated with cancer-specific survival. In multivariate analysis, TNM stage (III or IV : I or II; hazard ratio [HR], 12.322; P = 0.015), tumor differentiation (poorly differentiated : well or moderately differentiated; HR, 3.112; P = 0.021), and GPS (GPS 2 : GPS 0 or 1; HR, 5.168; P = 0.003) were identified as independent prognostic factors in colorectal cancer. CONCLUSION: Our study showed that the GPS was an independent variable from tumor stage and a good and convenient prognostic factor in colorectal cancer patients.

Matrix Metalloproteinase-2 and -7 Expression in Colorectal Cancer

PURPOSE: Matrix metalloproteinase-2 (MMP-2) and MMP-7 have been implicated in tumor growth and metastasis. This study aimed to investigate the expressions of MMP-2 and -7 in colorectal cancer and to evaluate their values as prognostic markers. METHODS: Immunohistochemical staining for MMP-2 and -7 was done in 144 resected colorectal cancer specimens. Clinicopathological data and survival results were compared with regard to the expression results. RESULTS: The expression rates of MMP-2 in tumor cells in the tumor center and the tumor border were 16.7% and 38.9%, respectively. That of MMP-2 in stromal cells was 27.8%. MMP-7 immunoreactivities of tumor cells in the tumor center and the tumor border were 6.9% and 23.6%. The expressions of MMP-2 and MMP-7 were correlated. MMP-2 expression in stromal cells was more increased in the distal part of the colorectum: 8.8% in right colon cancer, 29.5% in left colon cancer and 36.4% in rectal cancer. MMP-2 expression of tumor cells in the tumor border was correlated with T-stage. MMP-7 expression of tumor cells in the tumor border was increased in case of infiltrative cancer compared with fungating tumor. The expression patterns of MMP-2 and -7 were not correlated with other clinicopathological factors, including tumor markers, node metastasis, distant metastasis, lymphatic invasion, tumor differentiation, and recurrence. No significant associations between the overall and disease-free survival rates and the MMP-2 and -7 expression patterns were noted. CONCLUSION: The high expression rates of MMP-2 and -7 in tumor borders suggest that MMP-2 and -7 have some role in tumor invasion, but in this study, MMP-2 and -7 did not appear to be significant predictors of prognosis in colorectal cancer.

Solitary Fibrous Tumor That Developed in the Thigh

A solitary fibrous tumor (STF) is a relatively unusual neoplasm first described as a distinctive tumor arising from pleura. Some reports have shown that STF also affect extrathoracic regions. A 70-year-old woman was referred to our hospital for surgical treatment of an incidentally discovered thigh mass. We performed complete removal of the tumor. It was a soft tissue tumor with muscle indentation but without invasion to the surrounding muscles. The resected specimen was 7.0x6.3x5.2 cm. Histologically, the tumor was composed of a haphazard proliferation of spindle cells and epitheloid cells with hypercellularity and high mitotic activity. Immunohistochemistry showed positive immunoreactivity for CD34, CD99, bcl-2 protein, CD117, vimentin, smooth muscle actin and epithelial membrane antigen. We report, herein, on a rare case of malignant SFT in the thigh region along with a review of the literature.

Clinical Importance of Vimentin and MMP 2 Expression in Hepatocellular Carcinoma

BACKGROUND / PURPOSE: Hepatocellular carcinoma (HCC) is a common cancer with a poor prognosis. A better understanding of the molecular mechanisms underlying the genesis of HCC, as well as the progression of HCC, allow for improved prediction of the prognosis of patients with HCC and more effective treatment. In this study, we determined the expression of vimentin and matrix metalloproteinase 2 (MMP 2) and evaluated the clinical significance in (HCC). METHODS: Immunohistochemical staining was performed for vimentin and MMP 2 in 98 surgically resected HCC specimens using the tissue microarray method. The clinicopathologic data and the outcomes were reviewed, and the levels of expression of vimentin and MMP 2 were compared. RESULTS: Positive expression of vimentin and MMP 2 was observed in 7.1% and 41.8% of specimens, respectively. The overexpression of vimentin and MMP 2 had a positive correlation with tumor cell proliferative activity, as measured by the Ki-67 labeling index (p<0.001 and p=0.043, respectively), but was not correlated with the TUNEL labeling index. Other clinicopathological factors, such as platelet count, serosal invasion, Edomondson grade, capsule infiltration, TNM stage(UICC, 6th edition) and extrahepatic metastases in patients with recurrences had a significant correlation with vimentin. The presence of portal vein thrombosis approached statistical significance with MMP 2 expression. In the survival analysis, overexpression of vimentin and MMP 2 was correlated with a poor overall survival rate based on univariate analysis (p=0.002 and, p=0.047, respectively), but not based on multivariate analysis. CONCLUSION: In HCC, vimentin and MMP 2 may have a role in cancer progression with more aggressive potential, thus suggesting their use as a prognostic markers in HCC.

Occult Papillary Thyroid Carcinoma Presenting as a Cystic Neck Mass / 대한내분비외과학회지

The majority of cystic masses in the lateral neck are benign entities, and these entities include branchial cyst. Occult papillary thyroid carcinoma can occasionally present with regional lymph node metastasis. However, cystic metastasis from occult papillary thyroid carcinoma is a very rare condition. We present here a case of a cystic neck mass as the sole initial clinical manifestation of metastatic occult papillary thyroid carcionoma.

Prognostic Value of Erythrocyte Sedimentation Rate in Patients with Colorectal Cancer

PURPOSE: Prognostic indicators are used increasingly in clinical trials and to guide surveillance for patients with colorectal cancer (CRC). The significance of a preoperative, elevated erythrocyte sedimentation rate (ESR) as a predictive indicator for malignancy and for prognosis in colorectal cancer has not been elucidated. Hence, the current study was conducted to evaluate the ESR as a prognostic indicator in patients with CRC. METHODS: This study enrolled 232 patients who underwent surgery in our hospital between 1997 and 2004. ESR with clinicopathologic features and overall survival were evaluated retrospectively. RESULTS: The ESRs of 139 patients were elevated, and those of 93 patients were normal. Elevated ESR was associated with the male gender, decreased hemoglobin, increased platelet count, high preoperative CEA, high preoperative CA19-9, tumor size (> or =5 cm), T stage, and TNM stage. Patients with elevated ESR had poorer survival (P=0.001), but a multivariate analysis did not reveal an elevated ESR as an independent factor for prognosis. CONCLUSIONS: Preoperative elevation of ESR in patients with CRC suggests the presence of a tumor with aggressive behavior and a poor outcome.

The Prognostic Value of CA19-9 in Patients with Colorectal Cancer

PURPOSE: There has been much debate about the significance of the CA19-9 level for predicting the prognosis of colorectal cancer patients. This study aimed to evaluate the prognostic value of the preoperative serum CA19-9 level and the CA19-9 expression in the tumor tissues of colorectal cancer patients METHODS: One hundred patients with colorectal cancer and who had been treated by resection were studied. We assessed the correlations of the preoperative serum CA19-9 level and the status of the CA19-9 immunohistochemical staining with the clinicopathologic features, including the prognosis of the patients. RESULTS: The preoperative serum CA19-9 level had significant correlation with the status of CA19-9 immunohistochemical staining. The presence of distant metastasis was significantly correlated with an elevated level of serum CA19-9. The depth of tumor, the presence of lymph node metastasis, the TNM stage and tumor cell differentiation were significantly correlated with the status of the CA19-9 immunohistochemical staining. In addition, the gross morphology, depth of tumor, the presence of lymph node metastasis, the TNM stage, the status of the CA19-9 immunohistochemical staining and the serum CEA level were correlated with survival on univariate analysis. However, multivariate analysis did not validate the status of CA19-9 immunohistochemical staining as a significantly independent predictor of the prognosis. CONCLUSION: The CA19-9 expression was frequently observed in advanced stage tumor tissue, yet its expression in tumor tissue or the preoperative CA19-9 serum level did not show independent prognostic value for colorectal cancer patients.

Clinical Significance of Thrombocytosis in Patients with Colorectal Cancer

PURPOSE: Thrombocytosis is commonly associated with various tumors, including stomach, ovarian, lung, liver and pancreas cancers. Some clinical reports have shown thrombocytosis to be associated with the disease stage and prognosis. This study investigated the prevalence of the thromobocytosis in patients with colorectal cancer, and its association with the prognosis. METHODS: Two hundreds ninety-six patients with colorectal cancer who had been surgically treated at our hospital between 1997 and 2004 were enrolled in this study. The incidence, relationship with other clinicopathological factors, and the prognostic value of thrombocytosis were evaluated retrospectively. RESULTS: Thirty-seven of the 290 (12.8%) patients had thrombocytosis. The incidence of thrombocytosis was examined with regard to gender (P=0.018), tumor location (P=0.021), and T stage of tumor (P or =5 ng/ml) to be associated with both the disease-free survival (DFS) and overall survival (OS). Multivariate analysis revealed thrombocytosis to be significantly associated with the disease-free survival (P=0.026). CONCLUSION: Preoperative thrombocytosis appears to be an independent prognostic indicator of the DFS in patients with colorectal cancer.

Prognostic Value of Preoperative Serum Levels of CEA and CA19-9 in Patients with Colorectal Cancer

PURPOSE: The significance of serum levels of CEA and CA19-9 in forming a prognosis for colorectal cancer patients remains as subject for debating. The aim of this study is to assess their correlations with tumor pathology and their prognostic values. METHODS: We analysed the data on 274 patients with colorectal cancer who had been treated by resection from Jan. 1997 to Aug. 2005. Correlation of the preoperative serum values of CEA and CA19-9 with clinocopathologic features, including prognosis, of the patients was investigated. RESULTS: The positivity rates of the two tumor markes were significantly correlated with tumor size, differentiation, TNM staging, venous invasion, and neural invasion. In addition, the positivity rate of CEA was related to lymphatic invasion and that of CA19-9 to gender. In the univariate analysis, CEA (P<0.001), CA19-9 (P<0.001), tumor size (P=0.011), TNM staging (P<0.001), lymphatic invasion (P=0.003), venous invasion (P<0.001), neural invasion (P<0.001), and differentiation (P=0.023) correlated with survival of the patients. In the stepwise multivariate analysis, an advanced TNM stage (P<0.001), positive venous invasion (P=0.011), and positive neural invasion (P=0.013) were independent prognostic factors for poor survival. CONCLUSIONS: Our results demonstrated that high serum levels of tumor markers were associated with more aggressive cancers, but in the multivariate analysis, CEA and CA19-9 were found not to be independent prognostic factors.

CD40 and CD154 Expression in Hepatocellular Carcinomas

PURPOSE: CD40 expression has been reported in a variety of cells, including antigen presenting cells (dendritic cells), B lymphocytes, monocytes, and many epithelial malignancies (breast, lung, ovary, bladder, and melanoma). The interaction of CD40 and its natural ligand (CD154) is well known in the adaptive immune response. The CD40-CD154 pathway appears to have diverse effects in malignant disease. In this study, we investigated the expression of CD40 and CD154 and evaluated their clinical implication in hepatocellular carcinomas (HCC). METHOD: Immunohistochemical staining was performed for CD40 and CD154 in 96 surgically resected HCCs using the tissue microarray method. The clinicopathological data and outcomes were reviewed and compared to the expression of CD40 and CD154. RESULTS: Positive expression of CD40 and CD154 was observed in 64.2% and 37.5% of cases, respectively. Overexpression, defined by the stain intensity and area of CD40 staining had a positive correlation with tumor cell proliferation activity as measured by the Ki-67 labeling index (p=0.013) and CD154 had a similar tendency (p=0.094). CD40 overexpression was observed frequently in small sized HCCs (p=0.046). There were no other clinicopathological factors that were significantly correlated with CD40 and CD154 expression. CD40 overexpression was correlated with a poor overall survival according to the univariate analysis (p=0.054) and multivariate analysis (p=0.035). CD154 overexpression was not correlated with the overall survival rate. CONCLUSION: The results of this study showed that CD40 expression correlated with a more aggressive tumor potential in patients with HCC. CD 40 overexpression might provide a novel prognostic marker for survival in patients with HCC.

Neutropenic Enterocolitis after Chemotherapy for Colon Cancer

Neutropenic enterocolitis is observed in approximately 10~46% of patients with acute leukemia, as well as in patients with other diseases, like acquired immunodeficiency syndrom (AIDS), that lead to profound neutropenia. Patients who become neutropenic after combined chemotherapy are at special risk of developing neutropenic enterocolitis. With the recently increasing numbers of patients with solid tumors treated with high-dose chemotherapy, the frequency of this disease is expected to increase. However, this disease has been rarely reported in patients with colon cancer treated with leucovorin and 5-fluorouracil for adjuvant chemotherapy. We report a case of neutropenic enterocolitis after a treatment of 5-fluorouracil and leucovorin for sigmoid colon cancer.

Resection of Hepatic Metastasis of Gastric Cancer

PURPOSE: The benefit of surgical resection for hepatic metastasis from gastric cancer still remains unclear. We planned this study to estimate the surgical outcome of hepatic metastasis from gastric cancer. METHODS: Sixteen patients underwent hepatic resections for metastasis from gastric cancer between December 1991 and May 2005. We analyzed 11 patients who had no gross residual tumor after their operations. The clinical and pathological factors were evaluated with the surgical outcomes. RESULTS: Six patients had synchronous metastasis and 5 had metachronous metastasis. The number of hepatic metastases was one in 9 patients, two in 1 patient and four in 1 patient. There was no bilobar metastasis. The extents of the hepatic resections were 3 lobectomies, 4 segmentectomies and 4 wedge resections. There was no operative mortality. There was one postoperative complication, an intra-abdominal abscess, which was cured with percutaneous drainage. The mean survival was 18 months, the median survival was 13 months and the 1-year survival rate was 52.0%. One female patient is still alive 80 months after resection for metachronous hepatic metastasis. There was no statistically significant prognostic factor except for the patients' gender. (p = 0.0378) CONCLUSION: We consider that hepatic resection is a safe and valuable option for the treatment of metastatic gastric cancer.

Characteristics and Prognosis after Resection for Ruptured Hepatocellular Carcinoma

PURPOSE: A spontaneous rupture is a rare but life-threatening complication in patients with a hepatocellular carcinoma (HCC). Whether this condition has any influence on the subsequent outcome following a resection is unclear. Therefore, the long-term results of liver resection were compared in patients with and without a tumor rupture. METHOD: This retrospective study was conducted on 17 patients with a spontaneous rupture of an HCC out of 256 with an HCC who underwent hepatic resection. RESULTS: Reduced hemoglobin and albumin, as well as increased leukocytosis, a poor Child Class, large tumor and portal vein tumor thrombosis were more frequent clinical findings in patients with a ruptured HCC. The postoperative complication and extrahepatic recurrence rates were similar between the two groups. The 1- and 3- year survival rates in the 17 patients with a ruptured HCC were 41.2 and 17.7%, respectively, while these were 80.3 and 48.3%, respectively, in the 239 patients without a rupture. However, when these patients were compared exclusively with the 8 patients with a corresponding AJCC/UICC 6th ed. TNM stage IIIB disease without a rupture (50 and 0%, respectively), no significant difference was found in the overall survival rates between the groups. CONCLUSION: The surgical outcomes of stage matched patients with and without a ruptured HCC were similar.

Clinical Significance of Platelet Counts in Patients with Hepatocellular Carcinomas

PURPOSE: Thrombocytosis is reported in patients with various tumors, including stomach, colon, ovarian, lung and pancreatic cancers. Some clinical reports have shown thrombocytosis to be a poor prognostic factor in cancer patients. However, in hepatocellular carcinoma patients, the incidence and clinical significance of thrombocytosis have not been clearly verified. In this study, the clinical significance of platelet counts was investigated in patients with hepatocellular carcinomas. METHODS: 212 patients with surgically proven hepatocellular carcinomas were enrolled in this study. The incidence, relationship with other clinicopathological factors, and the prognostic value of thrombocytosis were retrospectively evaluated. RESULTS: The incidence of thrombocytosis (> or =400, 000/ul) was 2.8% (6/212). The platelet counts were elevated in patients with a large sized tumor (p< 0.001), advanced TNM stage (p=0.009) and gross tumor thrombi in the portal vein (p=0.009). There was no difference in the survival between patients with low and high platelet counts. CONCLUSION: The incidence of thrombocytosis in hepatocellular carcinoma patients was very low. The platelet counts were elevated in patients with advanced hepatocellular carcinomas, but no prognostic significance was shown in this study.

Ruptured Undifferentiated (Embryonal) Sarcoma of the Liver in an Adult

The undifferentiated (embryonal) sarcoma of the liver (USL) has previously been called malignant mesenchymoma, undifferentiated sarcoma and fibromyxosarcoma. USL was named as an entity by Stocker and Ishak in 1978 on the basis of an Armed Forces Institute of Pathology (AFIP) series of 31 cases. The USL is a rare primary neoplasm of a mesenchymal origin and it predominantly occurs in children. Stocker reported that it was fourth in frequency among the liver tumors of childhood, following hepatoblastoma, hemangioendothelioma and hepatocellular carcinoma. Although there has been controversy as to the most appropriate treatment, the studies have reported that long term survival is possible after complete surgical resection with or without perioperative chemotherapy. This tumor's frequency in the adult population is extremely low. We report here on a case of USL in an adult woman with the review of the relevant literature.

Surgical Treatment of Hepatocellular Carcinoma / 대한소화기학회지

Due to recent rapid advances in imaging modalities, there has been a marked increase in the early diagnosis of hepatocellular carcinoma (HCC). Also, the emergence of effective local treatment methods has lead to the necessity for a wider selection of therapeutic modalities depending on the individual characteristics of each patient, such as tumor factors and hepatic factors, rather than a single uniform approach. At present, accurate preoperative liver function evaluation is available, and in addition, increased knowledge of the liver anatomy through liver transplantation, and advances in postoperative patient care has subsequently decreased the morbidity and mortality rates significantly after surgery. Such newly developed techniques and acquired knowledge has allowed the surgical option to expand from the classical hepatic lobectomy to systematic subsegmentectomy. Not only for early HCC, but also for intermediate HCC and advanced HCC, hepatectomy has shown the best results in each stage of disease with regard to treatment goals. It is therefore thought that hepatectomy should always be considered as the main treatment method in the multimodality treatment of HCC, as long as the liver function reserve permits, to enhance the quality of life, increase survival, and to cure disease. The authors present here a summary of the role of surgical approaches in HCC with respect to recent increases in the detection of early stage disease, new therapeutic modalities, and a new staging system for HCC.

Expressions of HSP70 and HSP27 in Hepatocellular Carcinoma

The heat shock proteins (HSPs) are ubiquitous molecules induced in cells exposed to various stress conditions, including carcinogenesis. The HSP70 and HSP27 among HSPs are of special relevance in human cancer inhibiting apoptosis. The aim of this study is to investigate the expressions of HSP70 and HSP27 in hepatocellular carcinoma (HCC) in association to tumor cell proliferation and apoptosis. We examined the expressions of HSP70 and HSP27 by immunohistochemical staining in 71 cases of HCC, and then related their expressions to clinicopathologic parameters and expressions of p53, Ki-67 and Apotag. HSP70 and HSP27 were frequently stained in the cytoplasm and nuclei of tumor cells, but not in the non-neoplastic hepatocytes. Immunoreactivities of HSP70 and HSP27 were observed in 56.3% and 61.9% of HCCs, respectively. HSP70 immunoreactivity correlated with high Ki-67 labeling indices (LIs) (p=0.0159), large tumor size (p=0.0129), presence of portal vein invasion (p=0.0231), and high tumor stage (p=0.0392). HSP27 immunoreactivity significantly related with the subgroup of HBV-associated HCCs (p=0.0003), but not with the others. Both HSP70 and HSP27 immunoreactivities showed no relation to Apotag LIs or p53 immunoreactivity. In conclusion, expressions of HSP70 and HSP27 may play an important role in hepatocarcinogenesis, and especially HSP70 showed a close relationship to the pathological parameters associated with tumor progression and high Ki-67 LIs. Our results could be additional evidence that HSP70 expressions can contribute to not only hepatocarcinogenesis but also tumor progression by promoting tumor cell proliferation.

A Case of Heterotopic Pancreas in the Ampulla of Vater that Mimicked Distal Common Bile Duct Cancer

Heterotopic pancreas can be defined as the occurrence of pancreatic tissue at aberrant anatomic sites that lack vascular, neural and anatomic community with the pancreas. A minority of heterotopic pancreas elicit clinical signs or symptoms that can vary according to its location and size, and the involvement of the overlying mucosa. We report here on a case of heterotopic pancreas that was removed by pancreatoduodenectomy under the erroneous diagnosis of distal common bile duct cancer.

Expression of Vascular Endothelial Growth Factor (VEGF) in Papillary Thyroid Carcinoma

PURPOSE: Papillary thyroid carcinomas are hypervascular tumors. The tumor growth and their metastases are dependent on factors that stimulate vessel formation (angiogenesis). Vascular endothelial growth factor (VEGF) has been reported to play an important role in the angiogenesis in papillary thyroid carcinomas in terms of the clinicopathological prognostic factors. METHODS: The expression of VEGF in specimens surgically removed from 23 papillary thyroid cancer patients were examined by immunohistochemical methods. RESULTS: The rate of VEGF expression was 56.5% in the tumor cells. The degree of VEGF expression was significantly correlated with local lymph node metastases (P=0.029) and the tumor extent (P=0.036). However, the degree of VEGF expression did not correlate with any clinicopathological characteristics. CONCLUSION: VEGF expression can be a useful prognostic factor of papillary thyroid carcinomas.