Lymph-vascular Space Involvement Research Articles

Primary tumor SUVmax on preoperative FDG-PET/CT is a prognostic indicator in stage IA2-IIB cervical cancer patients treated with radical hysterectomy.

The objective of the present study was to investigate the prognostic value of 18F-fluoro-2-deoxy-D-glucose (FDG) uptake by primary tumors on positron emission tomography/computed tomography (PET/CT) in surgically resectable cervical cancer. A total of 59 patients with stage IA2-IIB cervical cancer who underwent preoperative FDG-PET/CT, followed by radical hysterectomy and lymphadenectomy, were included in the study. The maximum standardized uptake value (SUVmax) of the primary tumor was measured, and the association between the SUVmax and clinicopathological factors or patient outcomes was analyzed. The SUVmax was significantly higher in patients with an advanced stage, lymph node metastasis, lymph-vascular space involvement and large tumors. The overall survival (OS) and progression-free survival (PFS) of patients with a high SUVmax were significantly lower compared with patients with a low SUVmax, using an optimal cut-off value of 7.36 for OS and 5.59 for PFS obtained from receiver operating characteristic curve analysis. Similarly, OS and PFS in patients with a high SUVmax were significantly lower in 39 patients with stage IB using a cut-off value of 7.90 and 6.69 for OS and PFS, respectively. Finally, multivariate analyses showed that the SUVmax of the primary tumor was an independent prognostic factor for impaired PFS in all patients and those with stage IB alone. These findings demonstrated that a high SUVmax on preoperative PET/CT was correlated with unfavorable clinical outcomes in patients receiving radical hysterectomy, suggesting that the SUVmax of the primary tumor may be a prognostic indicator for surgically-treated, early-stage invasive cervical cancer.

Is It Possible to Perform Less Radical Surgery for Invasive Uterine Cervical Cancer?

Background/Aims: A retrospective analysis was performed to evaluate the possibility of less radical surgery for early-stage invasive uterine cervical cancer without compromising the oncological outcome. Methods: The analysis was performed on 175 patients with invasive uterine cervical cancer in FIGO stage IA2-IIB, all of whom underwent primary radical hysterectomy. Relationship of tumor size with the incidence of pathologic parametrial involvement and the pelvic lymph node metastasis were investigated. Results: Fifty-one patients had tumor size ≤2 cm and 124 had tumor size >2 cm. Patients with tumor size ≤2 cm had a significantly lower incidence of parametrial invasion (p < 0.0001), lymph node metastasis (p < 0.0001), lymph vascular space involvement (p < 0.0001) and recurrence (p = 0.0002) than patients with tumor size >2 cm. Five-year relapse-free survival rate was 98 and 73%, respectively (p = 0.0004). Conclusion: It is suggested that less radical surgery may be appropriate for some cases with tumor size <2 cm.

The Number of Positive Pelvic Lymph Nodes and Multiple Groups of Pelvic Lymph Node Metastasis Influence Prognosis in Stage IA-IIB Cervical Squamous Cell Carcinoma.

Background:Pelvic lymph node metastasis (LNM) is an important prognostic factor in cervical cancer. Cervical squamous cell carcinoma accounts for approximately 75–80% of all cervical cancers. Analyses of the effects of the number of positive lymph nodes (LNs), unilateral versus bilateral pelvic LNM and a single group versus multiple groups of pelvic LNM on survival and recurrence of cervical squamous cell carcinoma are still lacking. The study aimed to analyze the effects of the number of positive pelvic LNs and a single group versus multiple groups of pelvic LNM on survival and recurrence.Methods:We performed a retrospective review of 296 patients diagnosed with Stage IA–IIB cervical squamous cell carcinoma who received extensive/sub-extensive hysterectomy with pelvic lymphadenectomy/pelvic LN sampling at Peking University People's Hospital from November 2004 to July 2013. Ten clinicopathological variables were evaluated as risk factors for pelvic LNM: Age at diagnosis, gravidity, clinical stage, histological grade, tumor diameter, lymph-vascular space involvement (LVSI), depth of cervical stromal invasion, uterine invasion, parametrial invasion, and neoadjuvant chemotherapy.Results:The incidence of pelvic LNM was 20.27% (60/296 cases). Pelvic LNM (P = 0.00) was significantly correlated with recurrence. Pelvic LNM (P = 0.00), the number of positive pelvic LNs (P = 0.04) and a single group versus multiple groups of pelvic LNM (P = 0.03) had a significant influence on survival. Multivariate analysis revealed that LVSI (P = 0.00), depth of cervical stromal invasion (P = 0.00) and parametrial invasion (P = 0.03) were independently associated with pelvic LNM.Conclusions:Patients with pelvic LNM had a higher recurrence rate and poor survival outcomes. Furthermore, more than 2 positive pelvic LNs and multiple groups of pelvic LNM appeared to identify patients with worse survival outcomes in node-positive IA-IIB cervical squamous cell carcinoma. LVSI, parametrial invasion, and depth of cervical stromal invasion were identified as independent clinicopathological risk factors for pelvic LNM.

Role of hypoxia-inducible factor-1α, carbonic anhydrase-IX, glucose transporter-1 and vascular endothelial growth factor associated with lymph node metastasis and recurrence in patients with locally advanced cervical cancer.

The aim of the present study was to determine whether the expression of hypoxia-inducible factor-1α (HIF-1α), carbonic anhydrase-IX (CA-IX), glucose transporter-1 (GLUT-1) or vascular endothelial growth factor (VEGF) was associated with the clinicopathological characteristics, lymph node metastasis or progression-free survival of patients with cervical cancer. Tumor tissue samples were obtained from 54 cervical cancer patients who had undergone radical hysterectomy. The expression of HIF-1α, CA-IX, GLUT-1 and VEGF was analyzed by immunohistochemical staining. Of the 54 cases, 28 were positive for HIF-1α, 35 for CA-IX, 40 for GLUT-1 and 23 for VEGF. It was revealed that HIF-1α expression was correlated with tumor stage and histology, CA-IX expression with tumor stage, tumor size, lymph node metastasis and lymph-vascular space involvement, GLUT-1 expression with tumor stage and lymph-vascular space involvement, and VEGF expression with microvessel density. The multivariate regression analysis indicated that CA-IX expression and lymph-vascular space involvement were independent variables associated with lymph node metastasis. Progression-free survival was shorter for patients who were positive for CA-IX or VEGF expression than for those who were negative for CA-IX or VEGF expression. The progression-free survival of patients treated with radiotherapy or chemo-radiotherapy following radical hysterectomy was also shorter for patients with positive CA-IX expression. These findings suggest that CA-IX expression is a possible risk factor for lymph node metastasis and disease recurrence in locally advanced cervical cancer patients.

Overexpression of ANCCA/ATAD2 in endometrial carcinoma and its correlation with tumor progression and poor prognosis

This study aimed to explore the clinical significance of AAA+ (ATPases associated with various cellular activities) nuclear coregulator cancer-associated (ANCCA) protein expression in endometrial carcinoma (EC). Correlations of ANCCA expression with clinicopathological factors and prognosis of EC patients were analyzed. Expression of ANCCA was detected in EC from 207 patients along with corresponding normal endometrium specimens by immunohistochemistry. ANCCA immunoreactivity was overexpressed in EC cases compared with that in normal endometrium (P < 0.001). High ANCCA expression was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade, depth of myometrial invasion, lymph node metastasis, lymph vascular space involvement, and recurrence but not with age and histological type. Patients with high ANCCA expression exhibited significantly poorer overall survival (OS) and disease-free survival (DFS) than patients with low ANCCA expression (P = 0.001 and 0.002, respectively). Cox multivariate analysis showed that high ANCCA expression was an independent prognostic factor for both OS (hazard ratio (HR) = 4.954, 95 % confidence interval (CI) = 1.537-15.966; P = 0.007) and DFS of patients with EC (HR = 4.237, 95 % CI = 1.295-13.859; P = 0.017). We identified ANCCA protein expression as a novel independent poor prognostic indicator in EC.

Distribution pattern of lymph node metastases and its implication in individualized radiotherapeutic clinical target volume delineation of regional lymph nodes in patients with stage IA to IIA cervical cancer.

BackgroundTo study the distribution pattern of lymph node metastases of stage IA to IIA cervical cancer and to clarify the individualized clinical target volume delineation of regional lymph nodes (CTVn).MethodsA total of 665 cases with International Federation Gynecology and Obstetrics stage IA to IIA cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy were retrospectively reviewed. The clinicopathological factors related to lymph node metastases were analyzed using logistic regression analysis.ResultsPelvic lymph node metastases were found in 168 of 665 patients resulting in a metastasis rate of 25.3%. Binary logistic regression analysis showed that age, lymph vascular space involvement, and deep stromal invasion statistically influenced pelvic lymph node metastases (p = 0.017, < 0.001, < 0.001, respectively). Pathological morphology type, lymph node metastases of the obturator, the external iliac and internal iliac, and the para-aortic had a strong influence on lymph node metastases of the common iliac (p = 0.022, 0.003, < 0.001, 0.009, respectively). Tumor size and lymph node metastases of the common iliac were significantly related to lymph node metastases of the para-aortic (p = 0.045, < 0.001, respectively). Lymph node metastases of the obturator, the external iliac and internal iliac were strongly correlated to lymph node metastases of the circumflex iliac node distal to the external iliac node (CINDEIN; p = 0.027, 0.024, respectively).ConclusionsFactors related to lymph node metastases should be comprehensively considered to design and tailor CTVn for radiotherapy of cervical cancer. Selective regional irradiation including the correlated lymphatic drainage regions should be performed.

Abstract 4737: Role of hypoxia-inducible factor-1α, carbonic anhydrase-IX and glucose transporter-1 in cervical cancer

Abstract Objectives: Hypoxia can drive the tumor toward a more aggressive malignant phenotype through genomic and proteomic changes. Hypoxia-inducible factor-1α (HIF-1α) transactivates genes whose proteins allow metabolic adaptation to hypoxia, including carbonic anhydrase-IX (CA-IX) and glucose transporter-1 (Glut-1). This study aimed to determine whether the HIF-1α, CA-IX and Glut-1 were associated with clinico-pathological characteristics and progression-free survival in patients with cervical carcinoma. Methods: Under the written informed consent, tumor tissue samples were obtained from 54 patients with cervical carcinoma performed radical hysterectomy. The expressions of HIF-1α, CA-IX and Glut-1 were detected by immunohistochemical staining using paraffin-embedded sections. Results: CA-IX and Glut-1 expressions were found in cell membrane and cytoplasm, and HIF-1α expression was observed in cell nuclear. In 54 cases, the positive expression was observed in 28 cases for HIF-1α, 35 for CA-IX and 40 for Glut-1. The HIF-1α expression was related with clinical stage and histology, CA-IX expression was related with clinical stage, tumor size, lymph-node metastasis and lymph-vascular space involvement, and the Glut-1 expression was related with clinical stage and lymph-vascular space involvement. The multivariate regression analysis revealed that the CA-IX expression and lymph-vascular space involvement were the independent variable associated with lymph-node metastasis in patients with cervical cancer. Progression-free survival was shorter in patient with positive CA-IX expression compared to negative CA-IX expression. Conclusion: In cervical cancer patients, CA-IX expression is possible to be a risk factor for lymph-node metastasis and disease recurrence, it was suggested that pH regulation induced by CA-IX under hypoxic condition may be associated with lymph node metastasis. Citation Format: Keita Iwasaki, Hiromitsu Yabushita, Taiki Ueno, Akihiko Wakatsuki. Role of hypoxia-inducible factor-1α, carbonic anhydrase-IX and glucose transporter-1 in cervical cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4737. doi:10.1158/1538-7445.AM2014-4737

Abstract 4738: Clinicopathological roles of adiponectin receptor and leptin receptor in endometrial carcinoma

Abstract Objectives: To clarify the roles of adiponectin receptor (AdipoR) and leptin receptor (ObR) in endometrial carcinoma, expressions of AdipoR-1 and -2 and ObR in endometrial cancer were examined immunohistochemically and relationships to clinicopathological implications were also analyzed. Methods: Under the written informed consent, paraffin-embedded tissues were obtained from 77 patients with endometrial carcinoma and were stained immunohistochemically using antibodies against AdipoR-1, AdipoR-2 and ObR. Results: AdipoR-1, AdipoR-2 and ObR were localized predominantly in the cell membrane and cytoplasm of tumor cells and normal endometrial cells. In 77 cases of endometrial cancer, positive expression was observed in 46 cases (59.7%) for AdipoR-1, 47 cases (61.0%) for AdipoR-2 and 33 cases (42.9%) for ObR. Expression of AdipoR-1 was observed more in stage I cases, G1 tumours, tumors with shallow myometrial invasion, tumors negative for lymphovascular space involvement, cases negative for adnexal invasion, and cases with no lymph node metastasis. However, expressions of AdipoR-2 and ObR showed no relationship to any clinicopathological factors. Kaplan-Meier analyses revealed that progression-free and overall survivals were longer in cases with positive AdipoR-1 expression compared with negative AdipoR-1 expression. Conclusion: Poor expression of AdipoR-1 thus appears to be associated with tumour grade, myometrial invasion, adnexal invasion, lymph-vascular space involvement and lymph-node metastasis, as well as poor prognosis in endometrial cancer. Citation Format: Hiromitsu Yabushita, Keita Iwasaki, Taiki Ueno, Akihiko Wakatsuki. Clinicopathological roles of adiponectin receptor and leptin receptor in endometrial carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4738. doi:10.1158/1538-7445.AM2014-4738

CD44 expression in curettage and postoperative specimens of endometrial cancer.

BackgroundAdhesive molecules like CD44 are well defined key players in the metastatic cascade in many cancers, including endometrial cancer. They could play a role of markers of invasion, metastasis and prognostic factors.Aim of the studyThe aim of the study is to assess a possible role of the CD44 as a marker of invasion in endometrial cancer, both at the moment of preoperative workup and final staging.Materials and methodsAvailable for analysis were archival specimens of 51 patients who had underwent curettage and surgery between 2002 and 2007. An immunohistochemical study for CD44 expression was performed in curettage and postoperative specimens. Normal endometrium of 20 randomly chosen patients was used as a control group.ResultsIn endometrial cancer the expression of CD44 was significantly more intensive than in normal endometrium. In postoperative specimens, the CD44 expression was weaker in serous than in endometrioid cancer. There was no significant correlation between the adhesion molecule expression and clinicopathological features: grade,depth of invasion, cervical involvement, serosal and adnexal involvement, lymph-vascular space involvement, lymph node and distant metastases nor FIGO stage.ConclusionsAn increased expression of CD44 in endometrial cancer suggests its possible role in pathogenesis of this disease, however, it doesn’t seem to be crucial. Different expression of the CD44 in endometrioid and papillary-serous type may reflect different pathogenesis of these types of cancer. No statistically proved relation between the investigated molecule expression and clinicopathological parameters suggests scepticism about its use in diagnostic process of endometrial cancer.

Distribution pattern of circumflex iliac node distal to the external iliac node metastasis in stage IA to IIA cervical carcinoma.

This study aimed to investigate the metastatic rate of circumflex iliac node distal to the external iliac node (CINDEIN) and its associations with clinicopathological factors in patients with stage IA to IIA cervical cancer to determine whether dissection of CINDEIN had a role in surgery of these patients. Six hundred thirty-three patients with the International Federation of Gynecology and Obstetrics stage IA to IIA cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy were retrospectively reviewed. The metastatic rate and distribution of the pelvic lymph nodes (PLNs) and CINDEINs were analyzed. The PLN metastatic rate was 25.6% (162 of 633 patients). Sixteen of 162 node-positive patients had CINDEIN metastases. Only 1 patient without PLN metastases had positive CINDEIN nodes. Univariate analysis revealed that other PLNs (including lymph nodes collected from obturator, external iliac, and internal iliac regions) and lymph vascular space involvement were the risk factors of CINDEIN metastases (P < 0.05). Other PLN metastasis (odds ratio, 50.6; 95% confidence interval, 6.6-386.7) was an independent risk factor for metastasis to CINDEIN by binary logistic regression analysis. Circumflex iliac node distal to the external iliac node metastases seemed to occur secondarily to widespread PLN metastases. In early stage cervical cancer, removal of the CINDEIN as a routine surgical procedure might be omitted to reduce operation time and minimize surgical morbidity.

Clinicopathological roles of adiponectin and leptin receptors in endometrial carcinoma.

To clarify the roles of adiponectin receptor (AdipoR) and leptin receptor (ObR) in endometrial carcinoma, the expression of AdipoR-1 and -2 and ObR in endometrial cancer was examined immunohistochemically, and correlations with clinicopathological implications were also analysed. Paraffin-embedded tissues were obtained from 77 patients with endometrial carcinoma and were stained immunohistochemically using antibodies against AdipoR-1, AdipoR-2 and ObR. AdipoR-1, AdipoR-2 and ObR were localised predominantly in the cell membrane and cytoplasm of tumour cells and normal endometrial cells. In 77 cases of endometrial cancer, positive expression was observed in 46 cases (59.7%) for AdipoR-1, 47 cases (61.0%) for AdipoR-2 and 33 cases (42.9%) for ObR. Expression of AdipoR-1 was observed most in stage I cases, G1 tumours, tumours with shallow myometrial invasion, tumours negative for lymphovascular space involvement, cases negative for adnexal invasion and cases with no lymph node metastasis. However, the expression of AdipoR-2 and ObR showed no correlation with any clinicopathological factors. Kaplan-Meier analyses revealed that progression-free and overall survival times were longer in cases with positive AdipoR-1 expression compared with negative AdipoR-1 expression. Poor expression of AdipoR-1, thus, appears to be associated with tumour grade, myometrial invasion, adnexal invasion, lymph-vascular space involvement and lymph node metastasis, as well as poor prognosis, in endometrial cancer.

The impact of lymph vascular space invasion on recurrence and survival in patients with early stage endometrial cancer

The aim of this study was to determine impact of lymph vascular space involvement (LVSI) on recurrence and survival in early stage of endometrial cancer. From 1991 through 2010, all endometrial cancer patients at University Hospital of Bari, Italy were identified. The Log-rank test and Kaplan-Meyer methods were used for time-to-event analysis to evaluate the effects of on lymph vascular space involvement recurrence rate and survival time. Of the 560 endometrial cancer patients, 525 underwent primary surgery. Of those, 399 had early stage disease. Three hundred and forty women were not found to have LVSI, whereas 59 were found to have lymph vascular space involvement. Forty-nine (12%) patients developed a recurrence and 20 of them showed lymph vascular space involvement. The statistical analysis demonstrated that LVSI was strongly associated with a poor survival (P < 0.0001). Lymph vascular space involvement is associated with a high risk of recurrence and poor overall survival in early stage of endometrial cancer; therefore, the clinical decision to decide whether or not a patient with early stage endometrial cancer should receive adjuvant therapy should be included the evaluation of lymph vascular space involvement.

Basigin-2 is the predominant basigin isoform that promotes tumor cell migration and invasion and correlates with poor prognosis in epithelial ovarian cancer

BackgroundBasigin, which has four isoforms, has been demonstrated to be involved in progression of various human cancers. The aim of this study was to examine the prognostic value of basigin-2 protein expression in epithelial ovarian cancer. Furthermore, the function of basigin-2 in ovarian cancer was further investigated in cell culture models.MethodsImmunohistochemistry staining was performed to investigate basigin-2 expression in a total of 146 ovarian tissue specimens. Kaplan Meier analysis and Cox proportional hazards model were applied to assess the relationship between basigin-2 and progression-free survival (PFS) and overall survival (OS). Real-time PCR, RT-PCR and western blot were used to explore basigin-2, basigin-3 and basigin-4 expression in ovarian cancer cell lines and tissues. To evaluate possible contributions of basigin-2 to MMP secretion and cell migration and invasion, the overexpression vectors pcDNA3.1-basigin-2 and basigin-2 siRNA were transfected into HO-8910 and HO-8910 PM cells respectively.ResultsHigh basigin-2 expression was associated with lymph-vascular space involvement, lymph node metastasis and poor prognosis of epithelial ovarian cancer. Multivariate analyses indicated that basigin-2 positivity was an independent prognostic factor for PFS (P = 0.006) and OS (P = 0.019), respectively. Overexpression of basigin-2 increased the secretion of MMP-2/9 and cancer cell migration and invasion of HO-8910 cells, whereas knockdown of basigin-2 reduced active MMP-2/9 production, migration and invasion of HO-8910 PM cells.ConclusionsThe expression of basigin-2 might be an independent prognostic marker and basigin-2 inhibition would be a potential strategy for epithelial ovarian cancer patients, especially in inhibiting and preventing cancer cell invasion and metastasis.

Clinicopathologic Characteristics and Prognostic Factors in Patients with Operable HER-2 Overexpressing Breast Cancer

To study the relationship between clinical pathologic characteristics, treatment modalities and prognostic factors in HER-2 (Human Epidermal growth factor Receptor-2) overexpressed breast carcinoma. Major clinico-pathological factors including therapeutic modalities and survival status of 371 breast cancer patients with HER2 over-expression, teated at Yantai Yuhuangding Hospital from March of 2002 to December of 2010 were retrospectively studied, with special attention focused on survival-related factors. The median age of the total 371 patients in this study was 48 years at time of diagnosis, among which, the leading pathological type was infiltrating ductal carcinoma (92.5%); 62.8% presented with a primary tomor larger than 2 cm in diameter at diagnosis, 51.0% had axillary lymph node (ALN) metastases; ER (Estrogen receptor) /PR (Progesterone receptor) double negative occured in 52.8% of cases, and PCNA (proliferation cell nuclear antigen) (+ + +) was found in 55.1%. HER-2 overexpressed patients were usually in advanced stage when the diagnosis was made (72.8% at stages IIA~IIIC). The prognosis and survival were assessed in 259 patients with complete follow-up data. 5-year DFS (disease-free survival) and OS (overall survival) rate was 68.0% and 78.0% respectively. Univariate analysis revealed that age, tumor size, ALN metastases, LVSI (lymph-vascular space involvement), PCNA status, hormonal therapy, chemotherapy cycles, and HER-2 overexpression, correlated closely with the prognosis. ALN metastases, LVSI, PCNA status and chemotherapy cycles were independent predictors of survival. HER-2 overexpressed breast cancer has special clinical and pathological characteristics, with advanced clinical stages and high rate of ER/PR double negative. Lymph node metastases, LVSI, PCNA and chemotherapy cycles are independent predictors of prognosis.

Expression and Prognostic Significance of Wnt7a in Human Endometrial Carcinoma

Introduction. Wnt7a is a secreted glycoprotein that regulates normal cellular proliferation and differentiation as well as tumorigenesis and progression. However, less is understood about the role of Wnt7a in human endometrial carcinoma. The aim of this study is to investigate the expression and prognostic significance of Wnt7a in endometrial carcinoma. Methods. Wnt7a expression was immunohistochemically examined in 35 normal endometrium, 33 hyperplastic endometrium and 70 endometrial carcinomas. Results. Wnt7a expression was lower in endometrial carcinomas compared with that in normal and hyperplastic endometrium (P < 0.001). Wnt7a was inversely correlated with FIGO stage (P = 0.001), grade (P = 0.001), lymph node metastasis (P = 0.002), depth of myometrial invasion (P = 0.006), lymph vascular space involvement (P = 0.001) and peritoneal cytology (P = 0.013). There was a negative correlation between estrogen receptor (ER) and Wnt7a (r = −0.281, P = 0.019), and a positive correlation between progestogen receptor (PR) and Wnt7a (r = 0.249, P = 0.037). Patients with lost or reduced Wnt7a expression had poorer progression-free survival (PFS) and overall survival (OS) (P = 0.005 and P = 0.042, resp.) on univariate analysis. But on multivariate analysis, Wnt7a expression was not an independent prognostic factor for PFS or OS. Conclusions. Our results indicate that Wnt7a expression may serve as an important prognostic marker.

Proteomic biomarkers predicting lymph node involvement in serum of cervical cancer patients. Limitations of SELDI-TOF MS

BackgroundLymph node status is not part of the staging system for cervical cancer, but provides important information for prognosis and treatment. We investigated whether lymph node status can be predicted with proteomic profiling.Material & methodsSerum samples of 60 cervical cancer patients (FIGO I/II) were obtained before primary treatment. Samples were run through a HPLC depletion column, eliminating the 14 most abundant proteins ubiquitously present in serum. Unbound fractions were concentrated with spin filters. Fractions were spotted onto CM10 and IMAC30 surfaces and analyzed with surface-enhanced laser desorption time of flight (SELDI-TOF) mass spectrometry (MS). Unsupervised peak detection and peak clustering was performed using MASDA software. Leave-one-out (LOO) validation for weighted Least Squares Support Vector Machines (LSSVM) was used for prediction of lymph node involvement. Other outcomes were histological type, lymphvascular space involvement (LVSI) and recurrent disease.ResultsLSSVM models were able to determine LN status with a LOO area under the receiver operating characteristics curve (AUC) of 0.95, based on peaks with m/z values 2,698.9, 3,953.2, and 15,254.8. Furthermore, we were able to predict LVSI (AUC 0.81), to predict recurrence (AUC 0.92), and to differentiate between squamous carcinomas and adenocarcinomas (AUC 0.88), between squamous and adenosquamous carcinomas (AUC 0.85), and between adenocarcinomas and adenosquamous carcinomas (AUC 0.94).ConclusionsPotential markers related with lymph node involvement were detected, and protein/peptide profiling support differentiation between various subtypes of cervical cancer. However, identification of the potential biomarkers was hampered by the technical limitations of SELDI-TOF MS.

Temporal pattern of recurrence of stage I endometrial cancer in relation to histological risk factors

ObjectiveTo study the temporal pattern of endometrial cancer recurrence in relation to histological risk factors in a large multicenter setting. Methods843 patients with apparent stage I endometrial cancer were followed for a median time of 38 months, documenting all recurrences. Patients were stratified as high risk based on the presence of at least one of the established histological risk factors: high tumor grade, penetration to the outer half of the myometrium, lymphvascular space involvement, lower uterine segment involvement and non endometroid histology. Survival analysis, including Kaplan–Meier curves, log-rank tests and multi-variate Cox proportional hazard regression were used to evaluate the equality of recurrence-free distributions for different levels of risk. ResultsRecurrence was documented in 66 cases. The presence of one or more of the histological risk factors was associated with significantly shorter recurrence free survival, not attenuating over time (p < 0.001). Age-adjusted Cox regression model demonstrated a significantly decreased recurrence-free survival (HR = 2.8 95% CI 1.5, 5.1) in the presence of risk factors. ConclusionsIn patients with stage I endometrial cancer, the presence of histological risk factors is associated with a significantly higher recurrence rate, which does not attenuate over follow up time. This may allow for a selective approach in the follow- up of endometrial cancer patients.

Conservative Therapy in Microinvasive Adenocarcinoma of the Uterine Cervix is Justified: An Analysis of 59 Cases and a Review of the Literature

This study aimed to evaluate the treatment and follow-up in a large series of women with early cervical adenocarcinoma (AC), stages IA1 and IA2, and to perform an extensive review of the literature in an effort to ascertain whether conservative therapy is justified. Records of 59 cases of microinvasive AC diagnosed between 1987 and 2006 in the Rotterdam district, the Netherlands, were retrieved. Clinical and pathological data were reviewed and analyzed. A mesh review of all relevant literature concerning stage IA1 and IA2 was performed. Of all patients, 33 had stage IA1 and 26 stage IA2 cervical AC. Also, 42 patients were treated conservatively (ie, conization or simple hysterectomy) and 17 patients were treated radically (ie, radical hysterectomy/trachelectomy with lymph node dissection). Recurrence occurred in 1 patient (1.7%) with stage IA1 disease (grade 1 adenocarcinoma, depth 1.4 mm, and width 3.8 mm, with lymph vascular space involvement [LVSI]) treated by vaginal hysterectomy. The mean follow-up was 79.9 months. From the literature, pooling all data from patients with stage IA1 and IA2 AC, the risk of recurrent disease was 1.5% after conservative therapy and 2.0% after radical therapy. Extensive treatment such as radical hysterectomy with pelvic lymph node dissection or trachelectomy does not prevent recurrent disease. Patients with microinvasive AC should be treated identically to patients with SCC. In stage IA1 and IA2 AC, we recommend conservative therapy (by conization). In cases with LVSI, an additional lymphadenectomy is advised. For patients with stage IA2 AC with LVSI, a trachelectomy/radical hysterectomy with lymph node dissection should be considered.

Simple conization and lymphadenectomy for the conservative treatment of stage IB1 cervical cancer. An Italian experience

Objectives Simple conization represents a plausible treatment scheme for managing stage IA1-2 tumors conservatively. However its curative potential has not been widely exploited as regards stage IB1 lesions. Recent studies suggest that, in selected circumstances, patients with stage IB1 disease undergoing radical hysterectomy could have been safely cured by simple hysterectomy and even by cervical conization. Methods Patients with stage IB1 cervical cancer desiring conservative management underwent simple conization and pelvic lymphadenectomy in three Italian institutes. Results Thirty-six women received the conservative treatment since 1995 to 2010. Median age was 31 (range 24–40) years and median tumor size was 11.7 mm (range 8–25 mm). Adenocarcinoma was present in 12 cases (33%) and grade 3 neoplasia in 5 (14%). Lymph-vascular space involvement was detected in five patients (14%). Eleven had already a child while two had experienced an early abortion and a fetal loss at second trimester. After a median follow-up of 66 months (range 6–168) only one pelvic lymphnodal relapse was observed. Twenty-one pregnancies occurred in 17 patients and 14 live babies have been born (two preterm at 27 and 32 weeks) while one is ongoing. Three first-trimester miscarriages, one second-trimester fetal loss, an ectopic pregnancy and a termination of pregnancy have been recorded. Five patients decided to undergo hysterectomy after 3–12 years after conservative therapy: in one residual microinvasive adenocarcinoma was found. Conclusions Cervical conization represents a feasible conservative management of stage IB1 cervical cancer and shows a low risk of relapse, provided that patients are selected carefully. Conization would be suitable to treat stage IB lesions smaller than 15–20 mm. with pathologic negative lymphnodes.

Neoadjuvant chemotherapy for locally advanced cervical cancer reduces surgical risks and lymph-vascular space involvement

Neoadjuvant chemotherapy (NACT), which can reduce the size and therefore increase the resectability of tumors, has recently evolved as a treatment for locally advanced cervical cancer. NACT has been reported to decrease the risk of pathologic factors related to prognosis of cervical cancer. To further assess the effects of NACT on surgery and the pathologic characteristics of cervical cancer, we reviewed 110 cases of locally advanced cervical cancer treated with radical hysterectomy with or without NACT at the People's Hospital of Peking University between January 2006 and December 2010. Of 110 patients, 68 underwent platinum-based NACT prior to surgery (NACT group) and 42 underwent primary surgery treatment (PST group). Our results showed 48 of 68 (70.6%) patients achieved a complete response or partial response to NACT. Estimated blood loss, operation time, and number of removed lymph nodes during surgery, as well as complication rates during and after surgery were not significantly different between the NACT group and the PST group. The rates of deep stromal invasion, positive parametria, positive surgical vaginal margins, and lymph node metastasis were not significantly different between the two groups. However, the rate of lymph-vascular space involvement (LVSI) was significantly lower in the NACT group than in the PST group (P = 0.021). In addition, the response rate of NACT was significantly higher in the patients with chemotherapeutic drugs administrated via artery than via vein. Our results suggest that NACT is a safe and effective treatment for locally advanced cervical cancer and significantly decreases the rate of LVSI.