Background Tumor microenvironment has recently drawn attention in that it is related with tumor prognosis. Cancer-associated fibroblast also plays a critical role in cancer invasiveness and progression in colorectal cancers. Periostin (POSTN), originally identified to be expressed in osteoblasts and osteoblast-derived cells, is expressed in cancer-associated fibroblasts in several tissue types of cancer. Recent studies suggest an association between stromal overexpression of POSTN and poor prognosis of cancer patients.
Methods We analyzed colorectal cancer cases for their expression status of POSTN in tumor stroma using immunohistochemistry and correlated the expression status with clinicopathological and molecular features.
Results High level of POSTN expression in tumor stroma was closely associated with tumor location in proximal colon, infiltrative growth pattern, undifferentiated histology, tumor budding, luminal necrosis, and higher TNM stage. High expression status of POSTN in tumor stroma was found to be an independent prognostic parameter implicating poor 5-year cancer-specific survival and 5-year progression-free survival.
Conclusions Our findings suggest that POSTN overexpression in tumor stroma of colorectal cancers could be a possible candidate marker for predicting poor prognosis in patients with colorectal cancers.
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Background While MUC2 is expressed in intestinal metaplasia and malignant lesions, the clinico-pathological significance of MUC2 expression is not fully elucidated in gastric carcinoma (GC). Methods: The present study investigated the correlation between MUC2 expression and clinico-pathological parameters in 167 human GCs. In addition, to confirm the clinicopathological significance of MUC2 expression, we performed a systematic review and meta-analysis in 1,832 GCs. Results: MUC2 expression was found in 58 of 167 GCs (34.7%). MUC2-expressing GC showed lower primary tumor (T), regional lymph node (N), and tumor node metastasis (TNM) stages compared with GCs without MUC2 expression (p=.001, p=.001, and p=.011, respectively). However, MUC2 expression was not correlated with Lauren’s classification and tumor differentiation. In meta-analysis, MUC2 expression was significantly correlated with differentiation and lower tumor stage (odds ratio [OR], 1.303; 95% confidence interval [CI], 1.020 to 1.664; p = .034 and OR, 1.352; 95% CI, 1.055 to 1.734; p = .017, respectively) but not with Lauren’s classification, pN stage, or pTNM stage. Conclusions: MUC2 expression was correlated with a lower tumor depth and lower lymph node metastasis in our study; the meta-analysis showed a correlation of MUC2 expression with tumor differentiation and lower tumor depth.
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BACKGROUND In multiple lung cancers (MLCs), distinction between intrapulmonary metastases and multiple primary tumors is important for staging and prognosis. In this study, we have investigated histopathologic prognostic factors of patients with MLCs. METHODS Histologic subtype, size differences, lobar location, lymphovascular invasion (LVI), size of the largest tumor, nodal status, number of tumors, morphology of tumor periphery, and immunohistochemical profiles using eight antibodies, were analyzed in 65 patients with MLCs. RESULTS There was no significant difference in the survivals of patients with multiple primary tumors and intrapulmonary metastases, as determined by the Martini-Melamed criteria (p=0.654). Risk grouping by four histologic parameters, LVI, margin morphology, size differences, and lobar locations of paired tumors were prognostic. The patients with one or two of aforementioned parameters had significantly longer survival than those with three or four parameters (p=0.017). In patients with largest mass (< or =5 cm), the risk grouping was found to be an independent prognostic factor (p=0.022). However, differences in immunohistochemical staining were not related to patients' survival. CONCLUSIONS A risk grouping of MLC patients by using combinations of histologic parameters can be a useful tool in evaluating the survival of patients with MLCs, and may indicate clonal relationship between multiple tumors.
The cliniopathological analysis was done on the 104 cases of malignant melanoma diagnosed at the Seoul National University Hospital (SNUH) from 1984 to 1993. The basic clinical data and the pathological items were based on the New Mexico Melanoma Registry Worksheet. The results were as follows. The male to female ratio was 1 : 0.79. Primary cutaneous melanoma was more common in the male (M : F=1 : 0.56) but primary extracutaneous melanoma with slight female dominancy (M : F=1 : 1.25). The peak age was the 6th decade in both cutaneous and extracutaneous malignant melanoma. In 66% (35 cases) of primary cutaneous malignant melanoma, the primary site was located in the acral area (including cases of acral lentiginous and nodular type), of which 63% (41% of total cutaneous melanoma) was acral lentiginous type. Major components of tumor cells were epithelioid. Clark's level of tumor was III or more at the time of the first visit in the majority of the cases (85%). The incidence rate of extracutaneous melanoma was 34.6% (36 cases) among the primary melanoma, and the eyeball (17.3%) was the most prevalent organ. All these features suggest that the racial difference between the Korean and the Caucasian is evident and also that etiologic role of sun damage is not quite marked in the Korean. We also suggest that an early detection program is very important to cure this malignant tumor.
Membranous glomerulonephropathy (MGN) is the most common primary cause of the nephrotic syndrome in adults, accounting for about 20% of the cases in most series. MGN is idiopathic in the majority of cases, however approximately 25% of adults have identifiable causes (secondary MGN). To evaluate the clinical and pathologic characteristics of MGN, we reviewed the clinical data and renal biopsies from 141 cases of MGN. The mean age of the patients at biopsy was 43 years old, but patients of all age were seen (range from 3 to 76 years of age). There were 88 males and 53 females.
There were 99 idiopathic MGN cases and 42 secondary MGN cases. The associated causes of secondary MGN included hepatitis B infection (18 cases), SLE (10 cases), drugs (4 cases), post-transplantation MGN (5 cases), diabetes mellitus (4 cases), syphilis (1 case) and hepatitis B infection associated with rheumatoid arthritis. The prevalence of histologic stages by Ehrenreich and Churg was as follows. Stage I was 24 cases, stage II was 72 cases, stage III was 35 cases, and stage IV was 9 cases. All patients had proteinuria. Nephrotic syndrome was observed in 39%, edema in 73%, microscopic hematuria in 49%, gross hematuria in 28%, hypertension in 13%, and the serum creatinine level above 1.5 mg/dl was in 13%. Cases with glomerulosclerosis was observed in 45 cases with an increased percentage of glomerulosclerosis in the higher grade. Immunofluorescence (IF) examination showed predominantly granular IgG (118 cases) and C3 (84 cases) stainings along the glomerular capillary wall. In idiopathic MGN, sparse mesangial IF staining was noted up to 10% of the cases. However, mesangial IF staining in SLE was observed in 33%, hepatitis B infection in 28% and diabetes mellitus in 50%. An electron microscopic examination revealed subepithelial electron dense deposits of immune complex in all cases. The prevalence of mesangial and subendothelial electron dense deposit in idiopathic MGN was present in 19% and 6%, respectively. In SLE cases, mesangial and subendothelial deposits were observed in 78% and 56%, respectively. In hepatitis B infection, mesangial and subendothelial deposits were observed in 54% and 69%, respectively. In conclusion, immune deposits in the mesangium are scanty in idiopathic MGN, and if pronounced this should increase suspicion of underlying systemic diseases, such as SLE or other infectious diseases.
The incidence of a primary central nervous system (CNS) lymphoma in western countries is about 1% of all the intracranial tumors and has increased 2.2% over the last decade. A similar pattern of increased frequency is observed in Korea. Although most CNS lymphomas in western countries are high grade tumors carrying poor prognosis, the clinicopathologic features of the Korean CNS lymphoma have not been well studied. We report clinicopathological features of 18 cases of histologically proven primary brain lymphoma. The mean age of the patients was 50 years and there was no sex difference. The clinical and radiological characteristics included multiple site of occurrence, infrequent extracranial spread, and frequent seeding via cerebrospinal fluid. No patients were immune-compromised host. Of 18 cases, 15 cases were of B-lineage and 2 cases were of T-lineage. According to REAL classification, there were 12 cases of diffuse large B cell lymphoma, two cases of B cell lymphomas of small lymphoid cell, and two cases of peripheral T cell lymphoma, unspecified. The remaining subtypes were not subclassified because of inadequate material. Pleomorphic cytologic features and necrosis of varying extent were frequent in the cases of diffuse large B-cell lymphoma. These results suggest that overall clinicopathologic features of primary malignant lymphomas of the central nervous system in Korea are similar to those of western countries.
In this study of 64 cases of breast cancer with a clinical follow-up period of more than 5 years, several prognostic factors were evaluated. The purpose of this study was to determine whether any one parameter or group of parameters serves as adequate predictors of tumor behavior and patient's prognosis.
Several prognostic factors included clinicopathological variables (patient's age, histologic grade, status of lymph node (LN) metastasis, and tumor size), expression of estrogen receptor (ER), progesterone receptor (PR), p53, bcl-2 and CD44 by immunohistochemistry, and DNA ploidy pattern. The results showed that the expression of ER and PR had a significant inverse correlation with the histologic grade (ER, p=0.05; PR, p<0.05). The expression of p53 protein showed a significant relationship with high histologic grade of tumor (p<0.05). The expression of bcl-2 protein was preferably seen in low histologic grade of tumor (p<0.05) and significantly associated with ER positive or PR positive tumors (ER, p<0.05; PR, p<0.05). This results suggest that bcl-2 protein might play significant roles in ER and PR. The CD44 expression showed a significant relationship with tumor size (p<0.05). The large size and aneuploidy pattern of tumor had a tendency to be associated with shorter patient survival. Cox's multivariate analysis showed that overall survival was affected by LN metastasis because of the shorter survival in patients with LN metastasis. In conclusion, tumor size, DNA ploidy pattern, and LN metastasis were themselves significant predictors of breast cancer survival rate.
The E-cadherin, alpha-catenin, and beta-catenin expressions were immunohistochemically investigated in paraffin-embedded materials of 80 cases of colorectal adenocarcinomas. The staining similar to normal colorectal mucosa with preserved strong membranous staining pattern was considered normal or preserved expression. The X2 test was used to analyse the statistical correlation of cadherin/catenin expression with clinicopathologic parameters and the Breslow test for the correlation with survival length. Normal colorectal mucosa showed strong membranous expression of cadherin/catenin complex. The reduced E-cadherin, alpha-catenin, and beta-catenin expression were found in 53/80 (66.3%), 46/80 (57.5%), and 44/80 (55.5%) cases of colorectal cancers examined, respectively. There were significant correlations between E- cadherin and alpha -catenin (p=0.035), and between alpha-catenin and beta-catenin (p=0.013). The reduced E-cadherin expression was associated with histologic dedifferentiation, tumor depth, lymph node metastasis, clinical stage (p<0.05), poor clinical outcome in stage II (p=0.016) and the reduced alpha-catenin expression with lymph node metastasis and clinical stage (p<0.05). Reduced expression of two or more proteins was correlated with lymph node matastasis, histologic dedifferentiation, clinical stage, and survival (p<0.05). The present study demonstrates a significant down-regulation of E-cadherin and alpha-catenin expression in colorectal cancer is associated with tumor invasiveness, histologic dedifferentiation, lymph node metastasis, and clinical stage. These results suggest that E-cadherin and alpha-catenin may be useful markers of invasiveness, lymph node metastatic potential, and clinical stage and of value as prognostic markers in the earlier stage. Further studies are needed to confirm the prognostic value of these cadherin/catenin complex.
The retinoblastoma (Rb)/cyclin D1/p16 pathway is an important constituent of cell cycle regulation. Perturbations in this pathway due to a variety of genetic aberrations have been reported in many human cancers including breast cancer. We examined the significance of immunoexpression of p16 protein, cyclin D1 protein, Rb protein (pRb), and p53 protein in 128 cases of invasive breast carcinoma. The results were correlated with survival rate and clinicopathological variables, including age, histologic grade, lymph node status, tumor size, estrogen receptor (ER), and progesterone receptor (PR) content. Abnormal expressions of p16 and pRb which were defined as negative staining were seen in 21% and 43% of tumors, respectively. There was a significant inverse relationship between p16 and pRb expression. There was no correlation between p16 staining and any other parameters, including survival rate, cyclin D1, p53, and clinicopathologic variables. Surprisingly, there was a trend for tumors which were positive for pRb to be grade III ductal carcinomas. Cyclin D1 positivity was noted in 46% of cases. The expression of cyclin D1 protein was significantly higher in lower histologic grade, higher ER and PR expression. The expression of p53 protein showed a significant correlation with high tumor grade. In a Cox multivariate analysis, neither p16, pRb, cyclin D1 nor p53 was an independent predictor, but tumor size and lymph node status were independent predictors of patient outcome.
The purpose of this study is to obtain the clinicopathological characteristics of replication error-positive (RER ) gastric adenocarcinoma in Korean, and to identify the significance of RER in adenoma stage of gastric carcinogenesis. Microsatellite instability was examined at D2S71, D2S119, D3S1067, D6S87, D11S905, DM, AR, VWF, HPRT, and BAT-26 loci. Frameshift mutation of BAX gene was analyzed in RER tumors. Normal and tumor DNA of 76 cases of gastric carcinoma and 25 cases of adenoma were examined. RER was found in 8 of 76 cases (10.5%), and it was more frequently found in adenocarcinoma of female (17.7%) than those of male (4.8%).
The frequency of RER was not different between the histologic types, age of the patient, anatomical location of the carcinoma, and the stage. The RER found in adenoma suggests that RER contributes to the malignant transformation early in the adenoma stage of the gastric carcinogenesis. None of the RER tumors revealed frameshift mutation of the BAX gene.
Though basal cell carcinoma is the most frequent and increasing malignant tumor of the skin in Korea, its pathological analysis has been done only on the small numbers. So, we did a comprehensive pathologic study on the 283 patients with basal cell carcinoma diagnosed in the Department of Pathology, Seoul National(233cases) and Chung-Ang(50cases) University Hospital during 1975-1992. The age distribution was ranged from 15 to 84 years with highest incidence rate in the age group of 5th-8th decades and 83.7% of all patients were over 40 years of age. Sex difference was not noted. The most common site was face occuring in 235 out of 283cases(83.0%) especially in the eyelid(25.5%), nose(17.9%) and cheek(16.6%). The most frequent histopathologic type was solid type(54.0%) followed by mixed(23.9%), adenoid(7.5%), and metatypical(4.7%). Among 51 mixed type, all showed solid components with adenoid(51.0%) followed by morphea(25.5%) and metatypical type(13.7%). And among 14 recurrent cases, solid type is found in 50% of cases. The characteristic clinicopathological findings are solid arrangement of tumor cells with various histological pattern and predominant occurence on the face.
The dysplastic nevus is a rare form of melanocytic nevus in Korean people. During the past 5 years the authors experienced 5 cases in the St. Mary's Hospital and Kang Nam St. Mary's Hospital. The criteria and the histologic findings of dysplastic nevi are debated in the western literature. Clinically, all cases were greater than 5 mm in size with ill defined irregular borders and irregularly distributed pigmentation. Histopathologically, all cases showed numerous discrete individual nests of melanocytes located in the dermoepidermal junction and the papillary dermis and were characterized by extension of dermoepidermal component of the nevus at the "shoulder" beyond the dermal component of the nevus. There was no cytologic atypia of nevus cells in all cases. Our cases lacked personal or family history of malignant melanoma. Therefore, we believe our cases are nonfamilial, sporadic and benign nevi with no prognostic significance. A brief review of the literature and a discussion on the term "dysplastic" and clinicopathologic correlation are made.
A total of 66 cases of thymoma(57 surgically resected cases and 9 incisional biopsy cases) were reviewed with an attempt to correlate pathomorphologic features and clinical presentations. Criteria of benign or invasive thymoma were primarily determined by operative clinical and pathologic findings. Of them, 21 cases were invasive thymomas. The mean age of patients at the time of surgery was 47 years and it occurred largely in the sixth decade. Myasthenia gravis was accompanied in 29 cases(43%). One patient died during folow-up period, and five of the remainder suffered from recurrence. Microscopically, mixed type was the most common one(33 cases), being followed by predominantly epithelial type(17 cases) and predominantly lymphocytic type(16 cases).
Thirty four cases of thymomas were cortical type, 29 mixed type, and the remaining 3 medullary type. None of the histologic type were significantly correlated with tumor invasiveness, Myasthenia gravis was more frequently associated with mixed and cortical type, respectively.