Prediction of lymphovascular space invasion in patients with endometrial cancer

Objective: Predict the presence of lymphovascular space invasion (LVSI), using uterine factors such as tumor diameter (TD), grade, and depth of myometrial invasion (MMI). Develop a predictive model that could serve as a marker of LVSI in women with endometrial cancer (EC).Methods: Data from 888 patients with endometrioid EC who were treated between January 2009 and December 2018 were reviewed. The patients'' data were retrieved from six institutions. We assessed the differences in the clinicopathological characteristics between patients with and without LVSI. We performed logistic regression analysis to determine which clinicopathological characteristics were the risk factors for positive LVSI status and to estimate the odds ratio (OR) for each covariate. Using the risk factors and OR identified through this process, we created a model that could predict LVSI and analyzed it further using receiver operating characteristic curve analysis.Results: In multivariate logistic regression analysis, tumor size (P = 0.027), percentage of MMI (P < 0.001), and presence of cervical stromal invasion (P = 0.002) were identified as the risk factors for LVSI. Based on the results of multivariate logistic regression analysis, we developed a simplified LVSI prediction model for clinical use. We defined the “LVSI index” as “TD×%MMI×tumor grade×cervical stromal involvement.” The area under curve was 0.839 (95% CI= 0.809-0.869; sensitivity, 74.1%; specificity, 80.5%; negative predictive value, 47.3%; positive predictive value, 8.6%; P < 0.001), and the optimal cut-off value was 200.Conclusion: Using the modified risk index of LVSI, it is possible to predict the presence of LVSI in women with endometrioid endometrial cancer. Our prediction model may be an appropriate tool for integration into the clinical decision-making process when assessed either preoperatively or intraoperatively.     

MELF invasion in endometrial cancer as a risk factor for lymph node metastasis

Pavlakis K, Messini I, Vrekoussis T, Panoskaltsis T, Chrysanthakis D, Yiannou P & Voulgaris Z
(2011) Histopathology  58 , 966–973
MELF invasion in endometrial cancer as a risk factor for lymph node metastasis Aim: To investigate whether the microcystic, elongated and fragmented (MELF) pattern of myometrial invasion encountered in certain endometrioid endometrial carcinomas can be considered as a risk factor for lymph node metastasis. Methods and results: A total of 351 cases of total abdominal hysterectomy and bilateral salpingo‐oophorectomy with/without lymphadenectomy or lymph node sampling, performed for endometrioid endometrial adenocarcinoma, were included in this study. The existence of MELF invasion, vascular invasion, fibromyxoid stromal reaction and lymph node metastasis were recorded. Immunohistochemistry for endothelial and epithelial markers was performed on selected cases. MELF invasion was identified in 20 (10.81%) and 13 cases (13.13%) treated without and with lymphadenectomy, respectively. All these cases were either well or moderately differentiated carcinomas, stages IA–II (without considering lymph node status). Positive lymph nodes were detected in seven of 13 MELF‐positive (53.84%) and six of 86 MELF‐negative cases (6.97%) This observation was statistically significant. Of the seven MELF‐positive tumours with lymph node metastasis, three cases exhibited intravascular tumour emboli while four showed a fibromyxoid stromal reaction. Conclusion: MELF pattern invasion was found to be related statistically to lymph node metastasis. Nevertheless, further studies are needed in order to evaluate the clinical significance of this observation.     

Association between well-known histopathological criteria and overall survival in invasive ductal carcinoma

We investigated the effect of clinical features and well-known histomorphological parameters on survival of breast cancer. Material and methods: 44 patients with invasive ductal carcinoma were included in this study. We investigated the effect of age, breast cancer location (right/left), histological grade, largest diameter of the tumor, lymphovascular and perineural invasion on patient survival. IBM SPSS (Statistical Package for Social Sciences) 20 program was used for statistics. Cox proportional hazard regression model for survival analysis, log-log plot, life function graphs were used. Results were 95% confidence interval, significance (P < 0.05). Results: In univariate analysis, the left breast localization, high histological grade, large tumor size, lymphovascular invasion, perineural invasion has been shown that reduced the overall survival (P < 0.05). In multivariate analysis, only high histological grade, large tumor size and perineural invasion were identified as parameters negatively associated with patient survival (P < 0.05). On univariate and multivariate analysis, age was not associated with survival. Conclusion: The above results should be considered in the follow-up and treatment planning of invasive ductal carcinoma patients.     

Low Expression of EphB2, EphB3, and EphB4 in Bladder Cancer: Novel Potential Indicators of Muscular Invasion

PurposeEph receptors are differentially expressed in numerous malignant tumors. This study intended to analyze the roles of EphB receptors (EphB2, B3, and B4) in urinary bladder cancer.Materials and MethodsTissue microarray-based immunohistochemical analysis was used to investigate the expression patterns of EphB2, EphB3, and EphB4 in 154 bladder cancer specimens. Immunohistochemical staining was conducted examining the extent of stained cells and staining intensity. EphB was considered to be highly expressed when the intensity of staining was more than moderate in >25% of cells in the tissue section. Small interfering RNA (siRNA) was used to knock down EphB expression in bladder cancer cell lines (T24, 5637) to determine the effects of EphB on tumor cell invasion, proliferation, and migration.ResultsEphB receptors (B2, B3, and B4) were detected in 40.9% (EphB2, 63/154), 71.4% (EphB3, 110/154), and 53.2% (EphB4, 82/154) of bladder cancer specimens. Low expression of EphB2, B3, and B4 receptors were significantly associated with higher tumor grade (EphB2, p<0.001; EphB3, p=0.032; EphB4, p<0.001) and muscular invasion (EphB2, p=0.002; EphB3, p=0.009; EphB4, p<0.001). No obvious correlation was observed with other clinicopathological variables, such as age, sex, recurrence, lymph node involvement, metastasis, and overall survival. Inactivation of EphB receptors by siRNA transfection increased cell viability, tumor cell invasion, proliferation, and migration in comparison with untransfected cancer cells.ConclusionLow expression of EphB receptors (B2, B3, and B4) can be a predictive marker for muscular invasion of bladder cancer.     

Total Surface Area Is Useful for Differentiating between Aggressive and Favorable Multifocal Papillary Thyroid Carcinomas

PurposeThe purpose of the present study was to identify more useful parameters for predicting behaviors of multifocal papillary thyroid carcinoma (PTC).ResultsIn 588 PTCs, tumor multifocality was found in 179 PTCs (30.4%). Multifocal tumors were significantly associated with extrathyroidal extension, lymph node metastasis, and higher tumor stage grouping (p<0.001, p<0.001, and p<0.001, respectively). The rates of nodal metastasis increased with greater TSA and TTD in PTCs. Multifocal papillary thyroid microcarcinomas (mPMCs) with TSA >3.14 cm² had higher rates of nodal metastasis than mPMCs with TSA ≤3.14 cm² (p=0.038); however, there was no significant difference between mPMCs with TTD >1.0 cm and with TTD ≤1.0 cm (p=0.325). In addition, nodal metastasis was more frequent in mPMCs with TSA >3.14 cm² than in unifocal papillary thyroid microcarcinomas (uPMCs) (TD ≤1.0 cm) (p=0.002), but not overt unifocal PTCs (TD >1.0 cm) (p=0.244).ConclusionOur results suggest that mPMCs with TSA >3.14 cm² show more aggressive behavior than uPMCs and mPMCs with TSA ≤3.14 cm². TSA could be useful in distinguishing aggressive mPMCs from favorable cases.     

Long-term survival of endometrioid endometrial cancer patients

Introduction

To establish risk factors for onset and progression of endometrioid endometrial cancer still remains the aim of scientists. The aim of the study was to determine disease-free survival (DFS) and overall survival (OS) in women with endometrioid endometrial cancer.

Material and methods

A retrospective review of 142 patients with endometrioid endometrial cancer after surgery treated with adjuvant radiotherapy and/or chemotherapy in the Regional Cancer Centre in Lodz between 2002 and 2004 was performed. Clinical and pathological data were correlated with clinical outcome and survival.

Results

In 3 patients (2.1%) clinical progression was diagnosed during the treatment. In 23 patients (16.7%) after primary remission, relapse was diagnosed 2-56 months after treatment. DFS and OS were 81.7% and 83.1% respectively. Better DFS significantly correlated with larger number of pregnancies (> 1), stage I of the disease and optimal surgery. Lower stage of disease, pelvic lymph node dissection, optimal surgery and depth of myometrial infiltration ≤ 50% were independent prognostic factors for better OS.

Conclusions

The results of our study provided significant evidence that early detection of endometrioid endometrial cancer enables optimal surgery. It reduces the indications for adjuvant therapy in stage I of the disease, and makes the prognosis significantly better. Other clinical and pathological factors such as numerous pregnancies, pelvic lymphadenectomy, and depth of myometrial infiltration, although important, are of less significance. Further prospective, randomized studies are necessary to prove the role of these factors.     

Tumor border pattern and size help predict lymph node status in papillary microcarcinoma: A clinicopathologic study

ObjectiveLymph node metastasis occurs in a subset of papillary microcarcinoma patients. We aimed to analyze the differences between metastatic and non-metastatic papillary microcarcinomas in order to identify a high-risk subgroup that is likely to require more aggressive treatment.Materials and methods126 thyroidectomies with lymph node dissections (central ± lateral), diagnosed as papillary microcarcinoma, were reviewed.ResultsMean age of 126 patients (F/M = 3.3) was 42 years. Mean size of the largest tumor was 7 mm. Classical was the most frequently (89%) encountered subtype. Multiple histologic subtypes co-occurred in 19%. Lymphovascular invasion was present in 16% (n = 20). 55 (44%) and 71 (56%) cases were unifocal and multifocal, respectively. 90 cases (71%) were non-encapsulated with overall infiltrative tumor borders, whereas in 36 cases (29%), the tumor had a well-defined capsule. Among those, 23 (64%) had tumor capsule invasion. 47 (37%) cases had metastasis in lymph nodes. In univariate analysis, metastasis was associated with tumor size of >5 mm (p = 0.02), tumor burden of >5 mm (p = 0.03), lymphovascular invasion (p = 0.02) and non-encapsulation (p = 0.01). No associations were found regarding sex, age, histologic subtype, lymphocytic thyroiditis, tumor capsule invasion (in capsulated tumors), laterality and multifocality (p > 0.05). In multivariate analysis, lymphovascular invasion (p = 0.01, OR = 3.97, 95% CI 1.35–11.67), tumor size >0.5 cm (p = 0.031, OR = 2.92, 95% CI 1.10–7.71) and non-encapsulation (p = 0.033, OR = 2.85, 95% CI 1.08–7.51) were independent risk factors.ConclusionSize (largest tumor or sum of all foci) of >5 mm, non-encapsulation and lymphovascular invasion were independent predictors of LNM in PMs. Unifocal tumors metastasize the same as multifocal tumors, suggestive of the contribution of other factors. Patients with sporadically resected microcarcinomas should be carefully followed-up, especially those that harbor risk factors in histology.     

TRAIL protein expression in breast cancer cells correlates with nuclear grade

Introduction

TRAIL protein may serve as an escape mechanism for cancer cells from the immune response. The aim of the study was to assess whether the presence of TRAIL protein correlates with unfavourable prognostic factors in breast carcinoma.

Material and methods

The study group was composed of breast cancer patients treated surgically in the Department of Surgical Oncology, Medical University of Lodz, Poland, from January to December 2003. Inclusion criteria for the study were fulfilled by 117 women. The immunohistochemical study of TRAIL protein expression was performed in 118 breast carcinomas diagnosed in the study group. TRAIL protein expression was correlated with other variables: tumour size, lymph node status, grade, histological type of carcinoma, oestrogen and progesterone receptor status, HER2 expression, presence of lymphovascular invasion and age of the patient.

Results

Expression of TRAIL protein was present in 73% of breast carcinomas. The percentage of TRAIL-expressing breast carcinoma cells correlated with the nuclear grade (τ = 0.26, p < 0.05; Tau Kendall test). The intensity of TRAIL expression (intensity of staining) in breast carcinoma cells correlated with the nuclear grade (τ = 0.15, p < 0.05; Tau Kendall test). TRAIL expression in breast carcinoma did not correlate with other studied variables.

Conclusions

Our analysis revealed that expression of TRAIL protein in breast carcinoma cells correlates with nuclear grade of carcinoma.     

Type of vascular invasion in association with progress of endometrial cancer

Vascular invasion (VI) is a well‐established marker for lymph node metastasis and outcome in endometrial cancer. Our study explored whether specific types of VI, defined as lymphatic (LVI) or blood vessel invasion (BVI), predict pattern of metastasis. From a prospectively collected cohort, we conducted a case–control study by selecting three groups of endometrial cancer patients (n = 183): 52 with positive lymph nodes at primary surgery, 33 with negative nodes at primary surgery and later recurrence and death from disease, and 98 with negative nodes and no recurrence. All patients underwent hysterectomy with lymphadenectomy. Immunohistochemical staining with D2‐40 and CD31 antibodies was used to differentiate between BVI and LVI. By immunohistochemical staining, detection of VI increased from 24.6 to 36.1% of the cases. LVSI was significantly more often seen in patients with positive lymph nodes compared with patients with negative nodes (p = 0.001). BVI was significantly more often seen in node‐negative patients with recurrence compared with node‐negative patients without recurrence (p = 0.011). In multivariable analysis, BVI, age, and tumor grade were predictors separating patients with and without recurrence. Lymph node–positive patients showed more often LVI compared with lymph node–negative patients, while BVI seems to be a predictor for recurrent disease.     

Can we identify the group of small invasive (T1a,b) breast cancers with minimal risk of axillary lymph node involvement? A pathohistological and DNA flow cytometric study

The goal of this study was to identify a group of small (≤1 cm) breast cancers (T1a,b) with a particularly low probability of axillary lymph node metastases, where routine axillary staging may be unnecessary.We retrospectively analyzed 152 T1a,b breast carcinomas with axillary dissection surgically removed at Clinical Hospital Center Split (Croatia) in the period from 1997 to 2006. The analysis included 40 T1a,b cancers with, and 112 T1a,b cancers without axillary lymph node metastases. The basic morphological features of cancers were investigated histologically, while hormone receptors and HER2/neu were investigated immunohistochemically with an additional CISH analysis of HER2/neu 2+ cases. The ploidy and S-phase fraction were determined by DNA flow cytometry. The association of the investigated features with the likelihood of axillary lymph node metastases was analyzed by univariate and multivariate analysis.The univariate analysis showed that lymph node metastases were associated with tumor size (T1a/T1b; p = 0.026), histological type (ductal/non-ductal; p = 0.014), lymphovascular invasion (p < 0.001), HER2/neu expression (p = 0.04), ploidy (p = 0.027), and combined values of ploidy and S-phase fraction (p = 0.025). The lymphovascular invasion was the only independent factor associated with axillary nodal metastases (p = 0.01). In the group of T1a,b cancers without lymphovascular invasion, HER2/neu expression (p = 0.021) and combined values of ploidy and S-phase fraction (p = 0.016) were independent factors associated with axillary lymph node metastases.This study showed that diploid T1a,b cancers with low S-phase fraction, which are also without lymphovascular invasion and HER2/neu amplification, represented the group of cancers with a low probability of axillary lymph node metastases.     

Meta-analysis of Predictive Clinicopathologic Factors for Lymph Node Metastasis in Patients with Early Colorectal Carcinoma

The objective of this study was to conduct a meta-analysis to determine risk factors that may facilitate patient selection for radical resections or additional resections after a polypectomy. Eligible articles were identified by searches of PUBMED, Cochrane Library and Korean Medical Database using the terms (early colorectal carcinoma [ECC], lymph node metastasis [LNM], colectomy, endoscopic resection). Thirteen cohort studies of 7,066 ECC patients who only underwent radical surgery have been analysed. There was a significant risk of LNM when they had submucosal invasion (≥ SM2 or ≥ 1,000 µm) (odds Ratio [OR], 3.00; 95% confidence interval [CI], 1.36-6.62, P = 0.007). Moreover, it has been found that vascular invasion (OR, 2.70; 95% CI, 1.95-3.74; P < 0.001), lymphatic invasion (OR, 6.91; 95% CI, 5.40-8.85; P < 0.001), poorly differentiated carcinomas (OR, 8.27; 95% CI, 4.67-14.66; P < 0.001) and tumor budding (OR, 4.59; 95% CI, 3.44-6.13; P < 0.001) were significantly associated with LNM. Furthermore, another analysis was carried out on eight cohort studies of 310 patients who underwent additional surgeries after an endoscopic resection. The major factors identified in these studies include lymphovascular invasion on polypectomy specimens (OR, 5.47; 95% CI, 2.46-12.17; P < 0.001) and poorly or moderately differentiated carcinomas (OR, 4.07; 95% CI, 1.08-15.33; P = 0.04). For ECC patients with ≥ SM2 or ≥ 1,000 µm submucosal invasion, vascular invasion, lymphatic invasion, poorly differentiated carcinomas or tumor budding, it is deemed that a more extensive resection accompanied by a lymph node dissection is necessary. Even if the lesion is completely removed by an endoscopic resection, an additional surgical resection should be considered in patients with poorly or moderately differentiated carcinomas or lymphovascular invasion.

Graphical Abstract

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Relationship between parameters from virtual touch tissue quantification (VTQ) imaging with clinicopathologic prognostic factors in women with invasive ductal breast cancer

Objectives: To investigate the association of shear wave velocity (SWV) and its ratio (SWV ratio) using virtual touch tissue quantification (VTQ) imaging with clinicopathologic prognostic factors in women with invasive ductal breast cancer. Methods: 138 consecutive women with invasive ductal breast cancer, who were diagnosed by pathological examination, were recruited between September 2011 and October 2013. Clinicopathologic findings were investigated in each participant, including age, invasive size, lymph node status, histological grade, estrogen receptor (ER) expression, progesterone receptor (PR) expression and human epidermal growth factor receptor 2 (C-erbB-2) expression. SWV and its ratio (breast mass/adjacent breast tissue) were measured by the VTQ imaging, and univariate analysis and multivariate regression analyses were applied to investigate their relationship with all clinicopathologic abnormalities. Results: In univariate analyses, large mass size (P < 0.001), lymph node involvement (P < 0.001), High histological grade (P = 0.001) and C-erbB-2 expression (P = 0.029) were significantly associated with SWV, whereas large invasive size (P < 0.001), lymph node involvement (P = 0.001) and high histological grade (P = 0.007) were significantly related to SWV ratio. Multiple linear regression indicated that invasive size was the strongest pathologic determinant of SWV and its ratio (P < 0001). Conclusion: SWV and its ratio by the VTQ imagining were significantly associated with clinicopathologic abnormalities, and may therefore provide prognostic information in patients with invasive ductal breast cancer.     

Medullary breast cancer is a predominantly triple-negative breast cancer – histopathological analysis and comparison with invasive ductal breast cancer

IntroductionMedullary breast cancer (MdBC) is an uncommon type of breast cancer representing 1–7% of all cases. It is characterized by the occurrence of many histopathological features associated with a high grade of malignancy.Material and methodsTwelve MdBCs chosen from a group of 1,122 women suffering from invasive breast cancer were analyzed. Histopathological examination and analysis of a basic molecular profile, i.e. estrogen (ER), progesterone (PR) and HER2 receptor expression, and their comparison with invasive ductal breast cancer (IDC), were performed.ResultsMdBC accounted for 1.07% of all analyzed invasive breast cancer patients. All patients were female, with an average age of 58.54 years. The MdBC group exhibited a larger median tumor diameter (2.05 vs. 1.89 cm), although ≥ T2 tumors comprised 42% vs. 51% for IDCs. Women without regional lymph node involvement (pN0) (83%) formed the largest group. There was a statistically significant difference in the presence of nodal involvement between the studied groups (p < 0.001). Based on the histological grade of malignancy, the majority of MdBC comprised grade II tumors (G2) (93%). In general, MdBC showed statistically higher histologic grade (G1-G3) than IDC (p = 0.003). The 5-year overall survival rate of MdBC patients was 91%. Most MdBCs (92%) were triple-negative, whereas the remaining 8% were HER2 positive.ConclusionsMdBC presented at a younger age than IDC, had a higher histological grade, larger median size and less frequent regional lymph node involvement. Most MdBCs were triple-negative, whereas IDCs were predominantly luminal. Despite numerous aggressive pathological features of MdBC, its clinical outcome and overall prognosis are favorable.     

Fascin expression in colorectal carcinomas

PURPOSE

The purpose of this study was to investigate the significance of fascin expression in colorectal carcinoma.

METHODS

This is a retrospective study of 167 consecutive, well-documented cases of primary colorectal adenocarcinoma for which archival material of surgical specimens from primary tumor resections were available. We chose a representative tissue sample block and examined fascin expression by immunohistochemistry using a primary antibody against “fascin”. We calculated the “immunohistochemical score (IHS)” of fascin for each case, which was calculated from the multiplication of scores for the percentage of stained cells and the staining intensity.

RESULTS

Fascin immunoreactivity was observed in 59 (35.3%) of all cases with strong reactivity in 24 (14.4%), moderate reactivity in 25 (14.9%) and weak reactivity in 10 (6.0%) cases. Strong/moderate immunoreactivities were mostly observed in invasive fronts of the tumors or in both invasive and other areas. Fascin immunoreactivity scores were significantly higher in tumors with lymph node metastasis (p:0.002) and advanced stage presentation (p:0.007). There was no relation between fascin expression and age, gender, depth of invasion, distant metastasis or histological grade (p>0.05). There was a higher and statistically significant correlation between fascin immunoreactivity in the invasive borders of tumors and lymph node metastasis (r:0.747, p:0.005). In stage III/IV tumors, two-year survival was 92.2% in tumors without fascin immunoreactivity, and only 60.0% in tumors with a fascin IHS>10 (p:0.003).

CONCLUSION

These findings suggest that fascin is heterogeneously expressed in approximately one third of colorectal carcinomas with a significant association with lymph node metastasis, tumor stage and location. Moreover, these results indicate that fascin may have a role in the lymph node metastasis of colorectal carcinomas.     

Mixed Carcinoma as an Independent Prognostic Factor in Submucosal Invasive Gastric Carcinoma

Mixed carcinoma shows a mixture of glandular and signet ring/poorly cohesive cellular histological components and the prognostic significance of each component is not fully understood. This study aimed to investigate the significance of the poorly cohesive cellular histological component as a risk factor for lymph node metastasis and to examine the diagnostic reliability of endoscopic biopsy. Clinicopathologic characteristics of 202 patients who underwent submucosal invasive gastric carcinoma resection with lymph node dissection in 2005–2012 were reviewed. Mixed carcinoma accounted for 27.2% (56/202) of cases. The overall prevalence of lymph node metastasis was 17.3% (35/202). Lymphatic invasion (P < 0.001), family history of carcinoma (P = 0.025), tumor size (P = 0.004), Lauren classification (P = 0.042), and presence of any poorly cohesive cellular histological component (P = 0.021) positively correlated with the lymph node metastasis rate on univariate analysis. Multivariate analyses revealed lymphatic invasion, family history of any carcinoma, and the presence of any poorly cohesive cellular histological component to be significant and independent factors related to lymph node metastasis. Review of preoperative biopsy slides showed that preoperative biopsy demonstrated a sensitivity of 63.6% and a specificity of 100% in detecting the presence of the poorly cohesive cellular histological component, compared with gastrectomy specimens. The presence of any poorly cohesive cellular histological component was an independent risk factor associated with lymph node metastasis in submucosal invasive gastric carcinoma. Endoscopic biopsy had limited value in predicting the presence and proportion of the poorly cohesive cellular histologic component due to the heterogeneity of mixed carcinoma.     

Endometrial endometrioid adenocarcinoma: a pathologic analysis of 827 consecutive cases

We reviewed 827 consecutive cases of pure endometrial endometrioid adenocarcinoma (EEA) treated by hysterectomy to update the distribution of pathologic features. Tumor grade (reported in a 2-tiered system), depth of myometrial invasion, presence of cervical involvement, lymphovascular invasion (LVI), and evidence of extrauterine disease were recorded.The median age at diagnosis was 62 years (range, 30-94 years). The tumor was high grade in 94 cases (11.4%), invaded into the outer half of the myometrium in 249 (30.1%), was positive for cervical involvement in 171 (20.7%), and was positive for LVI in 182 (22.0%). Lymph nodes (sampled in 85 cases) were positive in 13 (1.6%), and ovarian metastases were present in 15 cases (1.8%). High tumor grade was significantly associated with deep myometrial invasion (P > .0001), cervical involvement (P = .0065), and LVI (P > .0001).EEA manifests most commonly with low tumor grade and without deep myometrial invasion. High tumor grade is significantly associated with deep myometrial invasion, cervical involvement, and LVI.     

Overexpression of eIF3e is correlated with colon tumor development and poor prognosis

EIF3e is a component of the eukaryotic translation initiation factor 3 (eIF-3) complexes, which is an essential factor for initiation of protein synthesis in mammalian cells. Translational control plays key roles in the complex mechanism of cancer development and progression. However, the clinical significance of eIF3e in colon cancer remains to be elucidated. We analyzed the eIF3e expression in a tissue microarray (TMA), which contained 173 colon cancer tissues paired with adjacent normal mucosa and lymph node metastasis. The expression of eIF3e was significantly elevated in colon cancer tissues in comparison with those in adjacent normal mucosa (P < 0.001) and lymph node metastasis (P < 0.001). The high expression of eIF3e in colon cancer was significantly correlated with tumor size (P < 0.001), lymph node involvement (P < 0.001), distant metastasis (P < 0.001), clinical stage (P < 0.001), histopathologic classification (P < 0.001), and vessel invasion (P = 0.036). Univariate and multivariate analysis revealed that eIF3e is an independent prognosis factor for overall survival and disease-free survival in colon cancer. Down-regulation of eIF3e in vitro inhibited colon cancer cell proliferation, clonality and promoted cell apoptosis. Taken together, high eIF3e expression may contribute to tumor progression and predict poor prognosis in colon cancer.     

Prognostic impact of histological grade and vascular invasion compared with tumour cell proliferation in endometrial carcinoma of endometrioid type

AIMS: The relative impact of different prognostic factors is important for endometrial carcinoma patients. The aim of our study was to examine the combined value of histological grade [International Federation of Gynaecology and Obstetrics (FIGO)] and vascular invasion in comparison with tumour cell proliferation assessed by mitotic count and Ki67. The recently proposed binary architectural grade was also evaluated, in addition to age, depth of myometrial infiltration and FIGO stage in our population-based series of 237 endometrioid carcinomas. METHODS AND RESULTS: The tumours were studied for several histological features, including FIGO grade, binary grade, vascular invasion, mitotic count, myometrial invasion and expression of Ki67. FIGO grade was significantly associated with all investigated histological features, including Ki67 expression. Vascular invasion was significantly more frequent in FIGO grade 3 tumours, and was associated with a diffusely infiltrative growth pattern, solid growth, necrosis and deep myometrial invasion. All variables showed a highly significant relationship with patient survival in univariate analysis. In multivariate models, FIGO grade, vascular invasion, and proliferation assessed by Ki67 expression all had independent prognostic influence in this population-based study. Comparing tumour cell proliferation (Ki67) with vascular invasion as a marker of metastatic spread, the latter had a stronger survival impact. CONCLUSIONS: Vascular invasion and tumour cell proliferation measured by Ki67 both had independent prognostic influence, and should be considered to identify aggressive tumours of the endometrioid subtype.