Lymph-vascular Space Involvement Research Articles

Prognostic factors in microinvasive cervical squamous cell cancer: long-term results

We examined tumor-related pathologic factors and cone-related characteristics to identify parameters related to recurrence in microinvasive squamous cell carcinoma of the cervix treated with conization. This is a retrospective study on 67 consecutive cases of microinvasive carcinoma of the cervix [depth of invasion (DI) < 3 mm] treated with conization. The mean follow-up was 121 months (range 72-276 months). Four (6%) invasive recurrences were observed. Presence of lymphvascular space involvement (LVSI) was significantly related with recurrences (P < 0.05). The mean distance between tumor margin and apex of the cone (apical clearance) was 10.6 mm (range 5-22 mm), and the mean distance between lateral border of the cone and tumor margin (lateral clearance) was 6.5 mm (range 1.7-15 mm). We adopted cut-off values of 10 and 8 mm for apical and lateral clearances, respectively. We found a statistically significant difference between apical clearance and recurrence rate (P < 0.02). The LVSI was, other than DI, an important prognostic factor. Apical clearance was significantly correlated with recurrence. The cone-related characteristics, other than tumor-related pathologic factors, could help the decision concerning the definitive therapy for microinvasive carcinoma of the cervix.

Prognostic factors in microinvasive cervical squamous cell cancer: long-term results

We examined tumor-related pathologic factors and cone-related characteristics to identify parameters related to recurrence in microinvasive squamous cell carcinoma of the cervix treated with conization. This is a retrospective study on 67 consecutive cases of microinvasive carcinoma of the cervix [depth of invasion (DI) &lt;3 mm] treated with conization. The mean follow-up was 121 months (range 72–276 months). Four (6%) invasive recurrences were observed. Presence of lymphvascular space involvement (LVSI) was significantly related with recurrences (P &lt; 0.05). The mean distance between tumor margin and apex of the cone (apical clearance) was 10.6 mm (range 5–22 mm), and the mean distance between lateral border of the cone and tumor margin (lateral clearance) was 6.5 mm (range 1.7–15 mm). We adopted cut-off values of 10 and 8 mm for apical and lateral clearances, respectively. We found a statistically significant difference between apical clearance and recurrence rate (P &lt; 0.02). The LVSI was, other than DI, an important prognostic factor. Apical clearance was significantly correlated with recurrence. The cone-related characteristics, other than tumor-related pathologic factors, could help the decision concerning the definitive therapy for microinvasive carcinoma of the cervix.

Lymphvascular space involvement: an independent prognostic factor in endometrial cancer

Purpose of investigation To evaluate whether lymphvascular space involvement (LVSI) is a risk factor for relapse of disease and lymph node metastasis in endometrial cancer. Methods From 1978 till 2003, 609 patients with epithelial endometrial cancer were treated at the Groningen University Medical Center. The association of LVSI and relapse of disease was evaluated in the total group of 609 patients and in a ‘low’ and ‘high’ risk stage I endometrial cancer group. In 239 surgically staged patients, the relation of LVSI and lymph node metastasis was investigated. Results The median age at diagnosis was 63 years (range 27–92 years) with a median follow-up of 58 months (range 0–236 months). More than half of the patients (56%) received adjuvant radiotherapy. LVSI was present in 123 patients (25,6%), and a prognostic factor for relapse of disease (multivariate analysis, P < 0.0001). In the ‘low’ and ‘high’ risk stage I endometrial cancer patients an increase of 2.6 times in relapse of disease was observed in the presence of LVSI. LVSI positive tumors were more likely to have metastasized to the pelvic lymph nodes (multivariate analysis, P = 0.001). In patients with proven negative nodes, LVSI was a prognostic factor for relapse of disease (univariate analysis, P = 0.02). Conclusion LVSI is a predictor of nodal disease and an independent prognostic factor for relapse of disease in all stages of endometrial cancer. Patients with stage I endometrial cancer with positive LVSI are at risk for relapse of disease and might therefore benefit from adjuvant therapy. Content The presence of lymphvascular space involvement (LVSI) in endometrial cancer is significantly and independently associated with an increased risk of pelvic lymph node metastases and/or relapse of disease.

Surgical–pathological predictors of disease-free survival and risk groupings for IB2 cervical cancer: do the traditional models still apply?

Objective. To evaluate how the independent predictors of recurrence for stage IB2 cervical cancers treated with up-front radical hysterectomy apply to established risk models. Methods. Patients with IB2 cervical cancers diagnosed from 1990 to 2000 were identified from tumor registries of two institutions. Patients were classified into risk groups: high-risk (HR) (positive nodes, parametria, or margins), intermediate-risk (IR) (positive lymph vascular space involvement (LVSI) with any cervical stromal invasion (CSI), or (−) LVSI and > middle- CSI), or low-risk (LR) (absence of HR or IR characteristics). Disease-free survival (DFS) was estimated by Kaplan–Meier method and comparisons between subgroups were studied by log rank. A Cox proportional hazards model was used to determine independent predictors of recurrence. Results. We identified 86 patients with stage IB2 tumors treated by RH. We found 34% of patients to be HR, 60% IR, and 6% LR. Of the 52 IR patients, 28 had (+) LVSI with superficial, middle, and outer 1/3 CSI, and 24 had (−) LVSI with middle or outer 1/3 invasion. Overall, postoperative adjuvant radiation (PRT) was used in 52% of the 86 patients, including 0/5 LR, 16/52 IR, and 29/29 HR patients. Univariate predictors of recurrence were pelvic nodal disease, (+) LVSI, (+) parametria, outer 1/3 CSI, and tumor size > 6 cm. Age, grade, histology, and the use of postoperative radiation were not associated with recurrence. Multivariate analysis identified LVSI as the only independent predictor of recurrence (RR 5.2, P = 0.03). Two-year DFS for LR, IR, and HR patients was 100%, 83%, and 60%, respectively. Only 4/24 (17%) IR patients with (−) LVSI got PRT compared with 12/28 (43%) of IR patients with (+) LVSI. The 2-year DFS for IR patients with (−) LVSI was 96%. IR (+) patients recurred more frequently with a 2-year DFS of 71%. Conclusions. Overall, 66% of patients with IB2 disease were classified as having low or intermediate-risk disease. IR patients with (−) LVSI and all LR patients did well with surgery alone. This study defines the independent importance of LVSI and questions the utility of published IR models when applied to stage IB2 cervical cancer.

Adjuvant chemotherapy as treatment of high-risk stage I and II endometrial cancer

Objective. This study was performed to define the subgroups of patients who benefit from postoperative adjuvant chemotherapy in stage I and II endometrial carcinoma. Methods. A retrospective review of 170 International Federation of Gynecology and Obstetrics (FIGO) stage I and II endometrial carcinoma patients treated between 1988 and 2000 at Niigata University Hospital was performed. All patients underwent surgery, of which 41 patients underwent adjuvant chemotherapy, consisting of intravenous cisplatin, doxorubicin, and cyclophosphamide. Multivariate analysis was performed for the prognostic factors and actuarial techniques were used for the survival and recurrence rates. Results. The patients were divided into low-risk and high-risk groups based on the number of prognostic factors (tumor grade G3, outer half myometrial invasion, lymph-vascular space involvement (LVSI), and cervical invasion). The 5-year disease-free survival and the 5-year overall survival for the low-risk group were 97.4%, and 100%, respectively, which were significantly better than 77.4% and 88.1% for the high-risk group ( P < 0.0001, P < 0.0001), respectively. Among high-risk group patients, the 5-year disease-free survival and the 5-year overall survival were 88.5% and 95.2% in 26 patients treated with adjuvant chemotherapy, and 50.0% and 62.5% in eight cases who underwent only surgery ( P = 0.0150, P = 0.0226). Disease recurrence occurred in 7 (20.6%) of 34 high-risk group patients. Four of seven recurrences occurred in patients who did not receive postoperative chemotherapy, in which all four were distant failure. In the remaining three patients who were in the CAP group, two had vaginal wall recurrence and only one had pulmonary recurrence. Three recurrences were also observed in the 133 low-risk group patients. Only isolated vaginal wall recurrence occurred in three patients without adjuvant chemotherapy after the initial surgery. Conclusions. There is possibility that postoperative adjuvant CAP may be omitted in surgical stage I or II endometrial cancer patients with 0 or 1 prognostic factor. The high-risk group of patients should be treated with postoperative adjuvant CAP to decrease distant failure and improve prognosis.

A comparison of prognoses of FIGO stage IB adenocarcinoma and squamous cell carcinoma

Objectives: The objective of this study was to compare clinical and pathologic variables and prognosis of FIGO stage IB adenocarcinoma and squamous cell carcinoma of uterine cervix.MethodsA retrospective review was performed of 521 patients with stage IB squamous cell carcinoma and adenocarcinoma of cervix who treated primarily by type 3 hysterectomy and pelvic and/or para-aortic lymphadenectomy at Hacettepe University Hospitals between 1980 and 1997.ResultsAge, tumor size, grade, depth of invasion, lymph node metastasis, parametrial, vaginal, and lymphvascular space involvement (LVSI) were not different between two cell types except number of the lymph nodes involved. Metastasis to three or more lymph nodes was significantly higher in adenocarcinoma. Overall and disease-free survival were 87.7%, 84.0% versus 86.4%, 83.1% for squamous cell carcinoma and adenocarcinoma, respectively (P&gt; 0.05). The rate and site of recurrence were not different between two cell types. Multivariate analysis of disease-free and overall survival revealed independent prognostic factors as tumor size, LVSI, number of involved lymph node, and vaginal involvement.ConclusionPrognosis of FIGO stage IB cervical cancer patients who were treated by primarily radical surgery was found to be same for those with adenocarcinoma and squamous cell carcinoma.

Serum tumor markers in the management of ovarian, endometrial and cervical cancer

CA 125 is the most reliable serum marker for ovarian carcinoma. Whereas its role in the screening of the malignancy is controversial, serum CA 125 assay is very useful for both the differential diagnosis of ovarian masses, particularly in postmenopause, and the monitoring of the response to chemotherapy and follow-up of patients with histologically proven ovarian carcinoma. Tumor-associated antigens other than CA 125, such as CA 19.9, CA 15.3 and TAG.72, firstly identified in gastro-intestinal or breast malignancies, have been detected also in tissue and serum samples from patients with ovarian carcinoma. In particular CA19.9 offers the advantage of high sensitivity for mucinous histotype, which often fails to express CA 125. Serum CA 125 correlates with the clinical course of disease better than the other antigens, and in patients with positive CA 125 assay at diagnosis the concomitant evaluation of CA 19.9 or CA 72.4 or CA 15.3 does not offer any additional benefit for monitoring ovarian carcinoma. Conversely, the serial measurements of these other antigens may represent an interesting biochemical tool for the management of patients with negative CA 125 assay. Serum αFP and βHCG are very useful in the preoperative evaluation and management of nondysgerminomatous ovarian germ cell tumors, whereas elevated serum inhibin levels can be detected in patients with granulosa cell tumors of the ovary. As for endometrial carcinoma, preoperative serum CA 125 levels correlate with stage, depth of myometrial invasion, histologic grade, cervical invasion, peritoneal cytology, lymph node status and clinical outcome. Moreover, serial CA 125 assay is a good indicator of disease activity and a useful biochemical tool for post-treatment surveillance of patients with endometrial carcinoma. SCC is the most reliable serum marker for squamous cell cervical carcinoma, and in patients with this malignancy pretreatment SCC levels are related to tumor stage, tumor size, depth of cervical invasion, lymph-vascular space involvement, lymph node status and clinical outcome. Serial SCC measurements parallel the response to radiotherapy and chemotherapy as well as the clinical course of disease after the completion of treatment. Serum CYFRA 21.1 seems to be less sensitive than serum SCC for squamous cell cervical carcinoma. Elevated CA 125 levels can be often detected in patients with cervical adenocarcinoma. The future for tumor marker research is represented by the emerging technologies of transcriptional profiling and proteomics.

Frozen section evaluation of cervical cold knife cone specimens is accurate in the diagnosis of microinvasive squamous cell carcinoma

Objectives The purpose of this study was to determine the accuracy of frozen section evaluation of cervical cold knife cone (CKC) specimens in the diagnosis of microinvasive squamous cell carcinoma (SCC). Methods Using ICD-9 codes for invasive and microinvasive carcinoma of the cervix, a medical record from 1986 to 1998 identified 110 potential study subjects. Society of Gynecologic Oncologists criteria including depth of invasion ≤3 mm and absence of lymph-vascular space involvement were utilized for the diagnosis of microinvasion. Twenty-seven patients met study criteria including a frozen section diagnosis of microinvasive SCC on a cervical CKC specimen at our institution. A pathologist, blinded to patient diagnosis, reevaluated the histologic findings, including grade, depth of invasion, and cell type. Results Median age of diagnosis was 41 years. Median follow up was 3.6 years. The median time for pathologic review was 28 min (range 15–44 min). Independent retrospective pathologic review of the permanent sections confirmed the diagnosis of microinvasion in 100% (27/27) of patients. No patient experienced a cervical SCC recurrence. At 10 years, disease-specific survival is 100%. Conclusions Frozen section is reliable in the evaluation of CKC specimens with microinvasive SCC: this may afford a simplified surgical approach in certain cases. This accuracy should not be assumed to apply to adeno- or adenosquamous carcinoma of the cervix. At our institution which relies heavily on intraoperative pathologic evaluation, utilizing frozen section diagnosis as the basis for definitive surgical approach did not negatively impact disease-free survival.

Endometrioid Adenocarcinoma of the Uterus: Surgico-Pathological Correlations and Role of Pelvic Lymphadenectomy

Introduction: In 1988, FIGO added lymph node surgery to the staging system for endometrial cancer. This change remains controversial to date. From our study we aim to determine the significance of surgico-pathological parameters of endometrioid carcinoma for pelvic nodal metastases and survival, as well as to study the role of pelvic lymphadenectomy in the surgical treatment of this disease. Materials and Methods: A retrospective study was conducted in 198 women with endometrioid carcinoma who underwent full surgical staging including pelvic lymphadenectomy. The multiple variant regression analysis and the multi-variant logistic regression analysis were applied in the analysis of relationship. Results: A positive correlation between nodal metastases and grade, myometrial invasion, peritoneal cytology, adnexal involvement, lymphvascular space involvement and tumour size was found. For survival, significant prognosticators were grade, myometrial invasion, peritoneal cytology, lymphvascular space involvement, adnexal involvement, associated atypia and pelvic nodal metastases. Thirty-five per cent of the patients had high risk of recurrence based on uterine pathological factors but were node negative. They were spared external beam radiation and its associated morbidities, and were treated with adjuvant vault brachytherapy instead. Six per cent of the patients would have been understaged based on uterine factors alone if pelvic lymphadenectomy had not been done. Conclusion: We infer that routine pelvic lymphadenectomy should be considered for all surgically fit patients with endometrioid carcinoma. The accurate staging will allow individualised adjuvant therapy and prevent understaging and overtreatment.

La préservation de la fertilité dans les cancers du col utérin de stade précoce

Objective. – Evaluation of surgical techniques leading to fertility preservation in patients with early cervical cancer. Patients and methods. – Carcinological and obstetrical follow-up of 95 patients treated with radical trachelectomy between 1987 and 2002 for a cervical cancer stage less than Ib2. Results. – Four recurrences were observed; all of these were in case of tumor more than 2 cm in diameter ( P = 0.002), and three of the four recurrences were in case of lymph-vascular space involvement ( P = 0.07). Among the 42 patients willing and able to procreate, 33 were pregnant. Fifty-six pregnancies were registered. The rate of late miscarriage was 19% and 34 living newborns were obtained. Conclusion. – In case of early cervical cancer, radical trachelectomy preserves fertility, leading to a good rate of living newborns without impairing the chances of survival.

Heparanase Expression and Angiogenesis in Endometrial Cancer

Human heparanase has been shown to function in tumor progression, metastatic spread, and tumor angiogenesis. The aim of the present study was to assess heparanase expression in endometrial cancer in correlation with neovascularization and clinicopathological factors. Forty endometrial cancers were obtained from previously untreated patients (median age 55.5, range 33–78 years). The expression of heparanase mRNA was evaluated using a semiquantitative reverse transcriptase-polymerase chain reaction. Tumor angiogenesis was assessed using microvessel counting. The Mann-Whitney U test, one-factor ANOVA test, and Spearman’s test were used to determine the relationship between heparanase expression, microvessel density, and clinicopathological parameters. The expression of heparanase mRNA was detected in 20 of 40 (50%) endometrial cancers, and was significantly correlated with FIGO stage IIIc (p = 0.0075), the presence of lymph-vascular space involvement (p = 0.0041), lymph node metastasis (p = 0.0049), and histological tumor grade (p = 0.0030). Microvessel density was also associated with FIGO stage IIIc (p = 0.027), the presence of lymph-vascular space involvement (p = 0.001), lymph node metastasis (p = 0.038), ovarian metastasis (p = 0.030) and histological tumor grade (p = 0.0030). Moreover, we found a strong positive correlation between heparanase expression and microvessel density (r² = 0.475, p = 0.0001). These results suggest that the expression of heparanase may influence different malignant behaviors in endometrial cancer.

Der Nachweis zytokeratin-positiver Zellen im Knochenmark von Patientinnen mit operablem Zervixkarzinom FIGO I - II

Der Nachweis zytokeratin-positiver Zellen im Knochenmark von Patientinnen mit soliden Malignomen gilt als Indikator für eine hämatogene Disseminierung von isolierten Tumorzellen (ITC) und ist mit einem erhöhten Risiko für das Auftreten von Fernmetastasen assoziiert. Es war Ziel dieser Studie, die Inzidenz und prognostische Relevanz von ITC im Knochenmark von Patientinnen mit einem Zervixkarzinom FIGO I - II zu überprüfen.

Stage Ia1 cervical squamous cell carcinoma: conservative management after laser conization with positive margins

Objective Cone margin status has been reported to be the most important predictor of recurrent disease in patients with cervical intraepithelial neoplasia (CIN) undergoing cervical conization. Our purpose was to evaluate the conservative management of selected patients with microinvasive (FIGO stage Ia1) squamous cell carcinoma who have been treated by cervical conization with positive margins. Methods Twenty-seven patients underwent KTP laser conization and vaporization for stage Ia1 squamous cell carcinoma followed by careful observation. Involved margins were diagnosed if CIN III or more was present at the ectocervical or endocervical margin and 7 patients formed the basis of the present study. Follow-up consisted of cytology, histology, and pelvic examination. Disease recurrence was defined as a histology diagnosis of CIN III or more on colposcopically directed biopsy or endocervical curettage. Results The endocervical margins were involved by carcinoma in situ in seven (26%) patients. No ectocervical margin involvement was detected. No lymph–vascular space involvement (LVSI) and confluent invasion were seen. All seven patients were free of recurrent disease during median follow-up of 4.0 (range 2.3–7.6) years. Conclusion These results suggest that laser conization and vaporization may be a reasonable treatment option in patients with microinvasive (FIGO Stage Ia1) squamous cell carcinoma despite positive cone margins without invasive disease when LVSI is not demonstrated.

CA 125 levels in the preoperative assessment of advanced-stage uterine cancer

Objective: The purpose of this study was too evaluate preoperative levels of CA 125 in for the prediction of advanced uterine cancer. Study Design: We conducted a retrospective analysis of the correlation of preoperative CA 125 with grade, depth of invasion, lymph vascular space involvement, lymph node status, and stage. Results: High CA 125 levels correlated with advanced-stage (P <.0001) and positive (P <.0001) lymph node status. High levels of CA 125 also correlated with the deepest myometrial invasion, the presence of lymph vascular space involvement, and the highest grade. Receiver-operator characteristic curves demonstrated that depth of invasion, lymph vascular space involvement, and grade accurately predicted advanced-stage disease 73%, 77% and 80% of the time, respectively. CA 125 levels, however, correctly predicted advanced stage 94% of the time. The sensitivity and specificity of a CA 125 cutoff level of 37 IU/mL were 95% and 90%, respectively, with a positive predictive value of 78% and a negative predictive value of 97%. Conclusion: CA 125 appears to be a significant independent predictor of positive lymph node status and the extrauterine spread of disease. (Am J Obstet Gynecol 2003;188:1195-7.)

Immunohistochemical expression of cyclin E in endometrial adenocarcinoma (endometrioid type) and its clinicopathological significance.

Cyclin E is known as a G1-S phase regulatory protein and its abnormal expression has been implicated in cellular proliferation. This study aimed to investigate the correlation of cyclin E expression with tumorigenesis of the endometrium, proliferative activity, and clinicopathological features of endometrial adenocarcinoma. Immunohistochemical staining for cyclin E in addition to cyclin-dependent kinase 2 (cdk2), Ki67, p27, and p53 was performed by the labeled streptavidin-biotin method on formalin-fixed, paraffin-embedded tissues of normal endometria (20 cases), endometrial hyperplasias (20 cases), and endometrial adenocarcinomas (endometrioid type) (127 cases). Positive staining was expressed as a labeling index (LI) based on percentages of positive nuclei in tumor cells. Immunohistochemistry showed that the nuclei of the cells were positive for cyclin E. Both proliferative and secretory endometria, and endometrial hyperplasia regardless of type were negligible for cyclin E expression. The expression in normal endometrium and hyperplasia was significantly less than that in endometrial adenocarcinomas (P<0.0001). LIs of cyclin E in well-differentiated, moderately differentiated, and poorly differentiated endometrial adenocarcinomas were 31.5+/-33.3%, 37.8+/-31.9%, and 51.1+/-30.8%, respectively. Cyclin E expression increased significantly more in histological grades. The LI of cyclin E in carcinoma was positively correlated with that of cdk2, Ki67, and p53 but not with p27. The cyclin E expression was correlated with myometrial invasion and lymph-vascular space involvement, but not with FIGO stage, lymph node metastasis, coexisting endometrial hyperplasia, estrogen receptor, progesterone receptor, and menopause. Cyclin E as a complex with cdk2 is associated with carcinogenesis and disease progression in endometrial adenocarcinoma, and might be a prognostic indicator of endometrial adenocarcinoma.

Should the Presence of Lymphvascular Space Involvement Be Used to Assign Patients to Adjuvant Therapy Following Hysterectomy for Unstaged Endometrial Cancer?

The authors conducted a retrospective review of the medical charts of all patients who underwent surgical treatment of invasive adenocarcinoma of the endometrium between 1998 and 2000 at the James Cancer Hospital of Ohio State University College of Medicine. Data from the records of 366 patients who had surgical evaluation of the pelvic lymph nodes were evaluated to investigate the association of lymphvascular space involvement (LVSI) and lymph node metastases from endometrial cancer. The median age at diagnosis was 62 years (range, 27-90). The histological diagnosis was adenocarcinoma in 316 women; 52 patients also had areas of nonendometrioid histology, including uterine papillary serous adenocarcinoma (N = 21 ), clear-cell carcinoma (N = 14), and mixed epithelial adenocarcinoma (N = 17). Forty-four percent of patients were grade 1, 29% were grade 2, and 27% grade 3. Tumor invasion was confined to the inner third of the myometrium in 25% of the women, to the middle third in 43%, and to the outer third in 32%. LVSI was seen in one fourth of the cases, and the mean number of lymph nodes removed was 21.6. Forty-six women (13%) had metastases to the pelvic nodes (pelvic nodes only, N = 32; pelvic and para-aortic nodes, N = 14). More than one third of the patients (245 of 366) had stage 1 disease, 29 had stage II, 80 had stage III, and 12 women were stage IV. Ninety-two patients (25%) had tumor emboli in the lymphvascular spaces of the myometrium, and 46 of these patients had metastatic disease in the pelvic lymph nodes (P <.001). After statistical analysis, the association of LVSI with lymph node metastases remained significant (P <.001). Myometrial invasion was also found to have a significant association with positive pelvic nodes (P <.05 for invasion into the inner third of the myometrium, P <.01 for invasion into the middle third, and P <.001 in the outer third). When both variables were compared, LVSI was significantly associated with deeply invasive tumors (P <.001). Multivariate analysis, which included LVSI, tumor grade, patient age, depth of tumor invasion, and lymph node yield, found depth of invasion and LVSI to be significant predictors of metastatic disease in the pelvic lymph nodes (P <.004 and P <.04, respectively).

Low risk endometrial cancer: a study of pelvic lymph node metastasis.

The aim of our study was to find preoperative or intraoperative pathologic indicators that would discriminate a subgroup of early corpus cancers that would not require lymphadenectomy. A retrospective review of the medical records of 107 patients with endometrioid adenocarcinoma, FIGO grade 1 or 2 tumor, myometrial invasion <or=50%, and no intraoperative evidence of macroscopic extrauterine spread was performed. Clinicopathologic risk factors were analyzed with Fisher 's exact test with regards to pelvic lymph node metastasis. The median age of the patients was 54 years. Pelvic lymph node metastasis was observed in five of 107 patients (4.7%), where two patients with small tumors of 2 cm or less had positive pelvic lymph nodes. The presence of positive pelvic lymph nodes did not correlate with depth of invasion, histologic grade, cervical invasion, peritoneal cytology, menopausal status, preoperative serum CA125 level, or primary tumor diameter. Only lymphvascular space involvement (P < 0.0001) was significantly correlated to pelvic lymph node metastasis. We suggest that all patients with endometrial cancer who are taken to the operating room for primary therapy should be prepared to undergo extended surgical staging, except when clinical or operative factors increase patients' morbidity.

Low risk endometrial cancer: A study of pelvic lymph node metastasis

The aim of our study was to find preoperative or intraoperative pathologic indicators that would discriminate a subgroup of early corpus cancers that would not require lymphadenectomy. A retrospective review of the medical records of 107 patients with endometrioid adenocarcinoma, FIGO grade 1 or 2 tumor, myometrial invasion ≤50%, and no intraoperative evidence of macroscopic extrauterine spread was performed. Clinicopathologic risk factors were analyzed with Fisher ′s exact test with regards to pelvic lymph node metastasis. The median age of the patients was 54 years. Pelvic lymph node metastasis was observed in five of 107 patients (4.7%), where two patients with small tumors of 2 cm or less had positive pelvic lymph nodes. The presence of positive pelvic lymph nodes did not correlate with depth of invasion, histologic grade, cervical invasion, peritoneal cytology, menopausal status, preoperative serum CA125 level, or primary tumor diameter. Only lymphvascular space involvement (P &lt; 0.0001) was significantly correlated to pelvic lymph node metastasis. We suggest that all patients with endometrial cancer who are taken to the operating room for primary therapy should be prepared to undergo extended surgical staging, except when clinical or operative factors increase patients' morbidity.

Should the presence of lymphvascular space involvement be used to assign patients to adjuvant therapy following hysterectomy for unstaged endometrial cancer?

Objective. Thegoal of this study was to determine the influence of LVSI (lymphvascular space involvement) on the risk of lymph node metastases from endometrial cancer.Methods. All patients with surgically staged endometrial cancer from 1998 to 2000 were identified from divisional databases. The influence of LVSI on the risk for nodal metastases was determined after controlling for tumor grade and depth of invasion, and comparisons were made with the chi(2) or Fisher's exact tests. Multivariable analysis was performed using a logistic regression model.Results. We identified 366 patients who fit the study criteria. Pathologically, 92/366 (25%) tumors had LVSI, and 46 patients (13%) had evidence of pelvic lymph node metastases. Cancers with LVSI were significantly more likely to have nodal disease (35/92 versus 11/274, P < 0.001). When controlled for tumor grade, the presence of LVSI led to an increased incidence of pelvic node metastases (P < 0.001 for all grades). When stratified by depth of invasion in thirds, the presence of LVSI led to a significantly increased chance of pelvic lymph node metastases (P < 0.05 for each strata). When tumor grade and depth of invasion were evaluated together, LVSI led to a significantly increased risk of pelvic node metastases in patients with deeply invasive tumors. In a multivariable analysis, LVSI led to a significantly increased risk for pelvic lymph node metastases (P < 0.05).Conclusion. LVSI leads to an independent and significantly increased risk for pelvic lymph node metastases. As such, the presence of LVSI may indicate the need for lymphadenectomy or adjuvant therapy for potential regional lymph node metastases in patients with unstaged endometrial cancer.

Angiostatin expression in endometrial cancer

Angiostatin is a potent inhibitor of neovascularization, tumor growth and metastasis. The expressions of angiostatin and vascular endothelial growth factor (VEGF) were immunohistochemically examined, along with microvessel density, in primary tumors obtained from 57 endometrial carcinoma patients with stage I disease. Angiostatin expression was not related to depth of myometrial invasion, histological grade or lymph-vascular space involvement. VEGF expression also had no relation to depth of myometrial invasion or histological grade, however, it was enhanced in tumors with lymph-vascular space involvement. Angiostatin expression did not correlate with VEGF expression. Microvessel density correlated with VEGF, but not angiostatin expression. Disease-free survival was longer in patients with angiostatin-positive tumors than in patients with angiostatin-negative tumors, but did not differ among patients with VEGF-negative and VEGF-positive tumors. No patients with angiostatin-positive and VEGF-negative tumors had recurrent disease. We concluded that negative-expression of VEGF and positive-expression of angiostatin are significant prognostic factors in endometrial carcinoma patients.