Lymphatic Permeation Research Articles

Clinicopathological features and medical management of early gastric cancer

BackgroundThe detection of early gastric carcinoma (EGC) has increased worldwide due to advances in endoscopic techniques and equipment. The aim of the current study was to compare the clinicopathological findings of patients with and without lymph node metastasis. MethodsA total of 440 cases of early gastric carcinoma in patients who underwent surgical procedures between 1981 and 2002 at Kochi Medical School were studied. ResultsLymph node metastasis was observed in 38 patients (8.6%) with EGC. Multivariate analysis identified 4 independent risk factors of lymph node metastasis: (1) submucosal invasion; (2) tumor diameter greater than 3.5 cm; (3) the presence of vascular invasion; and (4) the presence of lymphatic permeation. ConclusionFor patients with tumor size between 1 cm and 3.5 cm we would recommend endoscopic resection initially, with a consideration for additional surgical resection if microscopic vascular invasion or lymphatic permeation is demonstrated.

Decreased expression of claudin-1 is correlated with recurrence status in esophageal squamous cell carcinoma

Claudins are transmembrane proteins and major constitutes of tight junctions, and participate in the paracellular barrior and cellular connecting functions. They have been shown to be differentially regulated in malignant tumors and play a role in carcinogenesis and tumor progression. Recent studies have shown changes in expression of claudins during tumorigenesis. However, a causal relationship between claudin expression and cancer recurrent status has not been established. In this study, we examined 54 esophageal cancer cases to assess immunohistochemical expression patterns of claudin-1. Eleven (20.4%) of 54 cases had negative immunostaining for claudin-1. Decreased expression of claudin-1 was statistically correlated with recurrence status (P = 0.018). The cases with lymphatic vessel permeation showed reduced expression patterns of claudin-1 (P = 0.033). Decreased expression of claudin-1 was also correlated with short diseasefree survival (P = 0.0003) and overall survival (P = 0.0045). The results indicated that claudin-1 expression was correlated with the recurrence status and poor prognosis in esophageal cancer and claudin-1 expression may be a good indicator of recurrence in esophageal cancer.

Two Cases of the Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma

The diffuse sclerosing variant of papillary thyroid carcinoma (DSPTC) is a rare histological subtype characterized by diffuse involvement of one or both thyroid lobes, widespread lymphatic permeation, prominent fibrosis, squamous metaplasia, abundant psammoma body and lymphatic infiltration. This subtype usually occurs in young female, and exhibits a higher frequency of cervical and distant metastasis. DSPTC clinically resembles Hashimoto’s thyroiditis, and often delays the correct diagnosis. We experienced two patients with DSPTC: the one patient presented with a neck mass lasting for a month, and in the other patient, a thyroid lesion was incidentally found during a medical examination. (J Korean Endocr Soc 23:430~437, 2008)

MIXED INTESTINAL- AND DIFFUSE-TYPE HISTOLOGY IS A RISK FACTOR FOR LYMPH NODE METASTASIS OF SUBMUCOSAL INVASIVE GASTRIC CANCER

Background: Endoscopic submucosal dissection is expected to increase the number of node-negative submucosal invasive gastric cancers, particularly differentiated-type adenocarcinomas that can be treated conservatively. Methods: Two hundred and seven consecutive surgically treated cases of differentiated-type early gastric cancer with submucosal invasion were analyzed clinicopathologically. Comparison was made between patients with node-positive (n = 33) and node-negative cancer (n = 174). Whole sections of surgical specimens were reviewed and reclassified as pure intestinal type or mixed type. The intramucosal and submucosal components were also described histologically, and the depth of invasion from the muscularis mucosae as well as the width of submucosal invasion was measured. Results: Twenty-four of 33 (73%) node-positive cases were of the mixed type, whereas 71 of 174 (41%) node-negative cases were of the mixed type (P < 0.01). As for the intramucosal histology, the ratio of mixed-type was also higher in the node-positive group (58% vs 34%; P < 0.05). Other factors associated with lymph node metastasis were larger tumor size (P = 0.003), deeper submucosal invasion (P < 0.001) and wider submucosal extension (P = 0.004), and lymphatic permeation (P < 0.001). Multivariate analysis demonstrated that lymphatic permeation (P = 0.001, OR 4.76), and mixed-type histology (OR 2.56) were independent risk factors. Conclusions: Histological heterogeneity is a risk factor for metastasis of submucosal invasive gastric cancer to lymph nodes. Heterogeneity of mucosal components is also a significant risk factor and thus a good predictor of lymph node metastasis, potentially useful in distinguishing patients ineligible for conservative therapy.

Can the clinical outcome in state II colon carcinomas be predicted by determination of molecular marker expression?

Conventional staging procedures are often unable to precisely predict prognosis in colon cancer (CC). In this study, we set out to investigate the possible role of molecular/structural indicators involved in cell cycle regulation (Ki-67, p53), apoptosis (p53 and bcl-2) and tumour neoangiogenesis (anti-VIII factor) in predicting tumour behaviour and clinical outcome in stage II CC patients. Analysis of the above indicators was performed by immunohistochemistry on 162 CC patient samples with curative intention surgery. Clinicopathological data included tumour grade, vascular and nervous invasion, production of mucin, lymphatic permeation and carcinoembryonic antigen levels. p53 protein was overexpressed in 58%, bcl-2 overexpression in 21.5%, Ki-67 in 60.1% and anti-VIII factor stained positive in 40.16% of the cases. Multiple regression analysis showed that some molecular markers were correlated. A significant relationship was seen between p53 and Ki-67, and bcl-2 and p53, but there was no correlation between bcl2 and Ki- 67 overexpression. Stepwise regression selected Ki-67 and anti-VIII factor as the best combination of variables capable of predicting both disease-specific and diseasefree survival. Only Ki-67 and anti-VIII factor were shown to be useful for the prediction of outcome and recurrence rate in curatively treated CC patients. In conjunction with clinical and pathological staging, they may provide a stronger indication of clinical outcome than staging alone and help better select therapeutic options in CC patients.

Clinicopathologic Features of Adenocarcinoma at the Gastric Cardia: Is it Different from Distal Cancer of the Stomach?

Although the incidence of gastric cardia cancer is considerably less than more distal gastric cancer, the rate of occurrence is now increasing. The objective of this study was to evaluate and compare the clinicopathologic findings of gastric cardia and more distal stomach adenocarcinoma. Patients included in our study were those who underwent operations for gastric adenocarcinoma in our institute from 1981 to 2006, and who had undergone complete medical history, including history of daily alcohol consumption; smoking; body mass index; and pathologic examinations. A total of 843 patients were included in our study, and were divided into cardia and noncardia cancer groups. Among the 843 patients, 23 (2.8%) had gastric cardia cancer. There were no substantial differences in age, gender, body mass index, smoking, or alcohol consumption between the two groups. Mean size of cardia tumors was larger than noncardia tumors. Although noncardia cancer was often detected at an early stage, gastric cardia cancer was most often diagnosed at an advanced stage. Pathologically, cardia cancer was more invasive and had more lymphatic permeation and lymph node metastasis than noncardia cancer. Gastric cardia cancer occurs at a low incidence of only 2.8% of resected gastric cancers. Unlike cases of gastric cardia cancer in Western populations, body mass index is not associated with occurrence of gastric cardia cancer in our study. Because gastric cardia cancer appears more aggressive than noncardia gastric cancer, early diagnosis and intervention are important.

EVALUATION OF THE RISK FACTORS OF LYMPH NODE METASTASIS IN PT1 STAGE COLORECTAL CARCINOMA: INDICATION FOR AN ENDOSCOPIC MUCOSAL RESECTION

Aim: In the present study, we aimed to clarify the parameters that can be used for clinically relevant treatment decisions.Patients and methods: During the period from July 1985 to April 2005, 283 pT1 cancers were selected for this study. Risk factors for lymph node (LN) metastasis were evaluated as follows: endoscopic appearance, tumor size, location, lymphatic permeation, venous invasion, patterns of cancer invasion into the submucosal layer, and depth of vertical invasion in the submucosal layer.Results: Results of the logistic regression analysis from these significant parameters were as follows: infiltrating growth pattern (odds ratio: 12.63); lymphatic permeation positive (odds ratio: 5.726); sigmoid colon (odds ratio: 4.585); tumor size (odds ratio: 1.718). However, the leading edge of only one cancer with LN metastasis in the expanding growth group was also cribriform pattern.Conclusion: The invasive growth patterns of infiltrating growth, lymphatic permeation, tumor location of the sigmoid colon, and maximum tumor size were independent and significant risk factors for LN metastasis in our logistic regression analysis. In particular, the former three factors (infiltrating growth, lymphatic permeation and sigmoid colon) revealed high odds ratio and covered all cases of LN metastasis. From the results of our study, the indication for operative intervention after EMR in pT1 cancer is those lesions which possess at least one factor among the three (infiltrating growth, lymphatic permeation and sigmoid colon). Also, assessment of the leading edge with a cribriform pattern should be dealt with carefully.

USING A MULTIVARIABLE MODEL FOR PREDICTION AND DIAGNOSIS

USING A MULTIVARIABLE MODEL FOR PREDICTION AND DIAGNOSIS

Clinical significance of the loss of MATS1 mRNA expression in colorectal cancer

Human Mob as tumor suppressor 1 (MATS1) has been shown to play a crucial role in tumor growth by regulating cell proliferation and apoptosis. We evaluated the expression of MATS1 in colorectal cancer patients and assessed its clinicopathological significance. MATS1 mRNA expression in paired tumor/normal samples from 72 cases of colorectal cancer was evaluated, using real-time RT-PCR analysis. MATS1 protein expression was determined by immunohistochemical staining. MATS1 mRNA expression was significantly lower in tumor tissues than in normal colorectal tissues (p<0.05). Clinicopathologically, factors such as incidence of large tumor size, deep invasion, lymphatic permeation and liver metastasis were significantly more frequent in the low MATS1 expression group (p<0.05). Prognosis of the low expression group tended to be poorer than that of the high expression group. MATS1 protein expression was diminished in tumor cells compared with corresponding non-cancer colon epithelial cells. MATS1 mRNA expression is suppressed in tumor tissue and its low expression is associated with tumor growth, invasion and metastasis of colorectal cancer. Specifically, low MATS1 expression may be a good marker of liver metastasis, a life-threatening indicator for colorectal cancer patients.

Fatty acid synthase expression in squamous cell carcinoma of the tongue: clinicopathological findings

Overexpression of fatty acid synthase (FAS), the cytosolic enzyme responsible for the conversion of dietary carbohydrates to fatty acids, has been reported in several human malignancies and pointed as a potential prognostic marker for some tumors. This study investigated whether FAS immunohistochemical expression is correlated with the clinicopathological characteristics of oral squamous cell carcinoma (OSCC). The clinical features of 102 patients with OSCC of the tongue treated in a single institution were obtained from the medical records and all histopathological diagnoses were reviewed. The expression of FAS was determined by the standard immunoperoxidase technique in formalin-fixed and paraffin-embedded specimens and correlated with the clinicopathological characteristics of the tumors. Eighty-one cases (79.41%) were positive for FAS. Microscopic characteristics such as histological grade (P < 0.05), lymphatic permeation (P < 0.001), perineural infiltration (P < 0.05), and nodal metastasis (P < 0.02) were associated with FAS status. A significantly lower survival probability for patients with advanced clinical stage (log-rank test, P < 0.001), lymph nodes metastasis (log-rank test, P < 0.001), presence of vascular permeation (log-rank test, P = 0.05), and perineural invasion (log-rank test, P = 0.01) was observed in the studied samples. The expression of FAS in OSCC of the tongue is associated with the microscopic characteristics that determine disease progression and prognosis.

Clinical significance of pleural lavage cytology in non-small cell lung cancer: A meta-analysis

18031 Background: The clinical significance of pleural lavage cytology (PLC) in non-small-cell lung cancer (NSCLC) remains controversial. This study was performed to estimate the associations of positive PLC with the main clinicopathological characteristics, and its prognostic value. Methods: PLC studies were identified on Medline, supplemented by manual search of bibliographies and proceedings. Authors were contacted for updated information. The quality of the studies was evaluated, and the data were extracted. Pooled odds ratios (ORs) and pooled hazard ratios (HRs) with confidence intervals [95% CIs] were calculated to evaluate the association of positive PLC with clinico-pathological characteristics and survival respectively. Results: Nineteen articles assessing PLC in NSCLC were selected for this study after exclusion of repeated publications or reports with little clinical detail. Positive PLC was diagnosed in 10.2% (516) of a total of 5073 patients. Positive PLC was strongly associated with lymphatic permeation (OR 4.96 [3.29, 7.54]), pleural invasion (OR 4.38 [2.16, 8.89], and vascular involvement (OR 2.94 [1.99, 4.35]). It was also found to be associated with advanced T stage, N stage, and TNM stage. Positive PLC was more frequent in adenocarcinoma than in squamous cell carcinoma (OR 2.32, [1.51, 3.52]). It was relatively more common in moderately- and poorly-differentiated tumors than in well-differentiated tumors (OR 1.89 [0.86, 4.16]). No association was found between positive PLC and fine needle aspiration cytology (OR 1.04 [0.58, 1.81]). Positive PLC was associated with high overall recurrence (OR 2.51 [1.79, 3.53]), as well as high local recurrence (OR 3.85 [1.57, 9.44]) and distant recurrence (2.58 [1.76, 3.76]). In analysis of survival, the overall HR for mortality was 2.43 [1.87, 3.16], suggesting significantly poorer survival for patients with positive PLC. Conclusions: Positive PLC in NSCLC is strongly associated with several existing poor prognosticators including pleural invasion, lymphatic spread, and vascular involvement. It may indicate locally advanced disease with high risk of recurrence and poor survival. We recommend that the PLC test be included in future clinical trials of adjuvant therapy for patients with NSCLC. No significant financial relationships to disclose.

Socioeconomic status as an independent prognostic factor in node negative, stage I-II breast cancer patients

21129 Background: Many prognostic factors for breast cancer are known, of those, clinical , histological, genetical and the socioeconomic status are considered important for the outcome of these patients. The objective of our study vas to evaluate the Socioeconomic status as an independent factor for survival Methods: Clinical records of node negative clinical stage I- II patients treated at the institution from 1980 to 1996 were reviewed . We included those initially treated with surgery, available paraphine blocks, follow up of at five years (the ones that had no recurrence). They were divided in two groups: 1: Lower socioeconomic status, economically deprived and 2: medium low to high status. The slides were reviewed s and the blocks were processed for immuno-histochemistry: steroid receptors, Her-2, p 53 and CD 34. The analysis was performed with X2, , t test and log rank for difference in survival Results: A total of 81 patients were studied, 35 in group 1, and 46 in group 2. Mean age for groups 1 and 2 was of 52 (28–74) and 52.9 (28–83) years respectively (p=0.39). Were stage I in group 1 8, II-28. In Group 2 were stage I, 12, II-34 (p=0.87). Patients in both groups were treated with surgery alone, with radiotherapy, chemotherapy and/or hormone therapy, without statistical significance for treatment.Vascular or lymphatic permeation was observed in 20 and 22 patients from groups 1 and 2 respectively (p=0.40). Mean SBR was of 7.2 and 7.1 respectively for groups 1 and 2 (p=0.54) Estrogen receptor was present in 10 and 11 patients (p=0.63) and progesterone receptor in 8 and 6 (p0.25) for each group. Her-2 was over expressed in 12 and 17 patients from group 1 and 2, p53 in 6 and 14 respectively (p=0.17)and CD34 in 7 and 6 for both groups respectively ( p=0.40). Median survival was of 225 months for group 1 and not reached at 243 months for group 2, with 90.22% alive, p= 0.005 Conclusions: According to our results, in this group of well studied patients, the only significant factor observed that had an impact over survival was the socioeconomic status. None of the clinical, histological or genetical variables showed significance. We think that prospective studies with special emphasis on the socioeconomic status have to be carried out in order to try to explain the differences that we observed. No significant financial relationships to disclose.

14-3-3σ negatively regulates the cell cycle, and its down-regulation is associated with poor outcome in intrahepatic cholangiocarcinoma

The 14-3-3sigma gene has been implicated in G2/M cell cycle arrest by p53, and the loss of 14-3-3sigma protein expression has been reported in diverse human cancers. However, the role of 14-3-3sigma in the signaling pathway of the cell cycle in the progression of intrahepatic cholangiocarcinoma has not been well understood. To clarify the role of 14-3-3sigma, we examined the protein expressions of 14-3-3sigma, cyclin B1, and p53 in 93 cases of intrahepatic cholangiocarcinoma by immunohistochemical staining. We also examined the correlation between these expressions and survival rate and clinicopathologic factors such as sex, age, tumor grade (ie, pathologic differentiation, tumor size, lymphatic permeation, vascular invasion, perineural invasion, lymph node metastasis), and tumor stage. Positive 14-3-3sigma protein expression (>30% of tumor cells) was observed in 67.7% (63/93) of cases of intrahepatic cholangiocarcinoma and was inversely correlated with cyclin B1 expression. No correlation was found between 14-3-3sigma expression and p53 expression or clinicopathologic factors; however, decreased 14-3-3sigma expression was an independent prognostic factor by multivariate survival analysis (P = .0282). Extensive methylation of 14-3-3sigma was found by methylation-specific polymerase chain reaction and sequence; however, no significant correlation was detected between methylation states and protein expression. These results indicate that depressed 14-3-3sigma protein is involved in the uncontrolled cell cycle in intrahepatic cholangiocarcinoma and that the decreased expression of 14-3-3sigma protein is a significant indicator of poor prognosis for patients with intrahepatic cholangiocarcinoma.

Expression of C‐Myc mRNA in squamous cell carcinoma of the tongue

The aim of this study was to evaluate clinical significance of C-myc mRNA in patients with tongue cancer. C-myc mRNA expression was studied by RT-PCR in peripheral blood of 25 tongue cancer patients and 24 controls. C-myc protein expression was studied by immunohistochemistry. In tongue cancer patients, pretherapeutic C-myc mRNA expression was significantly higher as compared to controls. In tumor tissues, a trend of low expression of C-myc mRNA was noted as compared to pretherapeutic blood. The mean pretherapeutic C-myc mRNA level was lower in tobacco-users, in older patients, in keratinizing tumors, in tumors showed lymphocytic infiltration as well as in non-responders as compared to their respective counterparts. C-myc mRNA expression was lower in tumors showed lymphatic permeation and in patients with a habit of tobacco use. Further, low C-myc mRNA expression associated with poor prognosis. C-myc protein expression was noted in 72% of the tumors and an inverse correlation was noted between C-myc protein expression and disease stage. In early stage disease, an inverse correlation was noted while in advanced stage disease, a positive correlation was noted. In tongue cancer, downregulation of C-myc mRNA associated with advancement of the disease and worse prognosis.

Survival of second and multiple primary tumors in patients with oral cavity squamous cell carcinoma in the betel quid chewing area

We report the incidence, risk factor(s), and overall survival (OS) of second/multiple primary tumors (SPTs/MPTs) in oral cavity squamous cell carcinoma (OSCC) patients in betel quid chewing areas. Of 816 untreated OSCC patients who had radical surgery, 15.7% had either synchronous or metachronous SPTs. The SPTs (70.3%) were at the oral cavity. SPTs (18.8%) developed third primary tumors, with a significantly higher incidence in synchromous than metachronous SPTs (p=0.001). An optimal, but significantly lower, 5-year OS was observed in patients with SPTs/MPTs than without (54.0% vs. 67.2%, p=0.0195). By multivariate analyses, OSCC sub-sites (p=0.006) and lymphatic permeation (p=0.040) were independent risk factors for SPT rate. A significantly higher 5-year OS was observed in SPT patients receiving a second radical surgery at the oral cavity/soft palate than patients that did not (p=0.0001). A good survival rate can be obtained for OSCC patients with resectable SPTs/MPTs.

Evaluation of extratumoral lymphatic permeation in non-small cell lung cancer as a means of predicting outcome

Lymphatic permeation (ly) has been described as a potential prognostic factor for non-small cell lung cancer (NSCLC). The purpose of this study was to analyze whether evaluation of the presence or absence of ly and its location (ly 0: absent, N=464; ly 1: intratumoral, N=42; ly 2: extratumoral, N=52) provides an appropriate means of predicting the outcome of NSCLC. We investigated the clinical implications of ly in 558 consecutive patients with surgically resected NSCLC. Evaluation according to ly status showed that the recurrence-free survival (RFS) time of the ly 2 patients was significantly shorter than that of the ly 0 patients (P<0.0001), the ly 1 patients (P=0.0028). A significant difference in RFS time was also observed between the ly 0 patients and the ly 1 patients (P=0.0025). RFS time of the ly 0 patients was significantly longer than that of the ly 1 plus ly 2 patients (P<0.0001). We also evaluated the patients with pathological stage I disease (N=378) separately. The RFS time of the ly 2 patients (N=9) was significantly shorter than that of the ly 0 plus ly 1 patients (P<0.0001). In the nine ly 2 patients, six developed a distant metastasis within 1 year. A multivariate analysis revealed that ly status (ly 0 plus ly 1 versus ly 2) was an independent prognostic factor (P=0.0116), demonstrating the significant prognostic value of extratumoral lymphatic permeation in NSCLC. These results indicate that ly status is a good prognostic marker of poorer outcome in patients with resected NSCLC.

Evaluation of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography in gastric carcinoma: relation to histological subtypes, depth of tumor invasion, and glucose transporter-1 expression

Variable uptake of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) has been noticed in positron emission tomography (PET) studies of gastric carcinoma patients, with low uptake occurring especially in some particular histological subtypes and early carcinomas. But this phenomenon has not been adequately explained. The aim of the present study is to clarify FDG uptake in gastric carcinomas especially focusing on histological subtypes, the depth of tumor invasion, and glucose transporter-1 (GLUT-1) expression which is considered to be one of the major factors for higher FDG uptake in human malignant tumors. FDG-PET was performed on 35 preoperative patients with gastric carcinoma. Forty macroscopically distinguishable lesions on a surgical specimen were histologically classified into two subtypes: Cohesive type (papillary adenocarcinoma, tubular adenocarcinoma, and solid type poorly differentiated adenocarcinoma) or Noncohesive type (signet-ring cell carcinoma and non-solid type poorly differentiated carcinoma). GLUT-1 expression was immunohistochemically determined. Histological parameters (GLUT-1 expression, histological subtypes, the depth of invasion, lymphatic permeation, venous invasion and tumor size) were evaluated, and factors for FDG uptake (detectability and the degree) and GLUT-1 overexpression were determined by multiple regression analysis. Nineteen of 40 gastric carcinomas showed detectable FDG uptake (48%), multiple regression analysis revealed that both the depth of invasion and histological subtypes are independent factors that influence the detectable FDG uptake in gastric carcinoma (R2 = 0.66). GLUT-1 expression was seen from an early cancer stage and the cohesive type was an independent factor influencing the overexpression of GLUT-1 (R2 = 0.66). GLUT-1 expression was the most influential factor for the degree of FDG uptake in gastric carcinoma (R2 = 0.68). This study provided important information on the clinical application of FDG-PET in gastric carcinoma that early or non-cohesive gastric carcinoma may show lower FDG uptake. Therefore, the usefulness of FDG-PET for the detection of gastric carcinoma is limited. But there is a possibility that FDG uptake associated with GLUT-1 expression may serve as a prognostic factor of gastric carcinoma representing tumor metabolism.

Intrahepatic sarcomatoid cholangiocarcinoma of round cell variant: a case report and immunohistochemical studies

Sarcomatoid transformation was observed in 4.5% of autopsied cases of intrahepatic cholangiocarcinoma. Here, we report a case of intrahepatic sarcomatoid cholangiocarcinoma with round cell feature, extremely rare variant. An 87-year-old man was incidentally found to have a tumor in the left lobe of the liver by abdominal computed tomography scans. The patient was clinically diagnosed to have intrahepatic cholangiocarcinoma and received palliative care without specific treatment. He died of hepatic insufficiency 3 months after the diagnosis. The autopsied liver specimens showed a reddish gray tumor of 4.0x2.8 cm in size. Histologically, the tumor was centrally hemorrhagic and necrotic and was composed of tubular adenocarcinoma and a round cell component, which has an eccentrically located nucleus and eosinophilic cytoplasm without mucin production. Immunohistochemically, the adenocarcinoma cells expressed cytokeratin 19 and beta-catenin in their cytoplasm, with E-cadherin and CD44s at the plasma membrane. In the round cells, cytokeratin 19 and vimentin was detected in their cytoplasm and CD44s at the plasma membrane. E-cadherin immunoreactivity was weakly present in their cytoplasm and beta-catenin was negative. Loss or reduction of the E-cadherin and beta-catenin expressions and overexpression of CD44s in the round cells are suggested to be contributed to the high propensity for lymphatic permeation and poor prognosis.

Carbonic anhydrase IX expression is associated with tumor progression and a poor prognosis of lung adenocarcinoma

Carbonic anhydrase (CA) IX catalyzes the hydration of carbon dioxide into carbonic acid and participates in a variety of physiological and biological processes. The aim of this study was to evaluate the prognostic significance of CA IX expression in patients with lung adenocarcinoma. Standard immunohistochemical techniques were used to study CA IX expression in 134 patients who underwent curative resection for adenocarcinoma of the lung at our hospital between January 1995 and December 1996. We evaluated the correlations between CA IX expression levels on cancer cells and clinicopathological factors. CA IX expression was not observed in normal lung tissue or specimens from non-invasive adenocarcinomas. CA IX immunostaining was detected in 33 (24.6%) invasive adenocarcinoma cases. Poor differentiated histological phenotype (p=0.0015), pathological stage (p=0.0400), vascular invasion (p=0.0009) and lymphatic permeation (p=0.0050) were significantly related to CA IX expression. On univariate analysis, CA IX positive cases showed significantly shorter overall survival (p=0.0083) and disease-free survival (p=0.0122). In particular, the overall and disease-free survivals in stages I+II were significantly shorter in the CA IX positive than in the CA IX negative cases (p=0.0269 and 0.0011, respectively). Our results suggest that CA IX expression is strongly associated with tumor progression and indicates a poor prognosis for patients with stages I+II lung adenocarcinoma.

Front pattern of invasion in squamous cell carcinoma of the penis: New prognostic factor for predicting risk of lymph node metastases

Objectives Treatment of penile carcinoma is based on excision of the primary tumor and regional lymphadenectomies. Lymph node metastasis is the most important prognostic factor, yet it cannot be reliably evaluated by imaging studies or clinical examinations; thus, new prognostic factors such as the pattern of invasion must be investigated. Methods The data of 112 patients with penile carcinoma who underwent amputation and lymphadenectomy were analyzed. The clinicopathologic variables were studied, in addition to the front pattern of invasion according to the standards established by the modified criteria of Anneroth and Bryne first used as a part of a prognostic score in squamous cell carcinoma of the oral cavity. The pattern of invasion expresses the tumor-host tissue relationship, demonstrating the infiltrative tumor characteristics. This pattern was defined as infiltrating (invasion in blocks of small solid strands of cell tumors that broadly infiltrated the organ’s stroma) and pushing infiltration (tumor cells have invaded large cell blocks with well-defined tumor-host interfaces). Results The variables that were significantly associated with the presence of lymph node metastases on univariate analysis were clinical N stage ( P = 0.011), lymphatic permeation ( P <0.001), venous embolization ( P = 0.025), and the pattern of invasion ( P <0.001). In the multivariate model, the lymphatic permeation, clinical N stage, and invasion type were independent risk factors for lymph node metastases. The follow-up varied from 0.1 to 452.8 months (mean 76.9, median 27.3). Conclusions Lymphatic permeation, clinical N stage, and standard infiltrating invasion were independent prognostic variables for the risk of lymph node metastasis.