Altered CD44 Variant 6 Expression in FIGO Stage IB Cervical Carcinoma

OBJECTIVE: CD44 is an adhesion molecule which plays an important role in metastatic cascade by mediating tumor cell interaction with the endothelium and the subendothelial matrix. In this study CD44v6 expression was immunohistochemically investigated on 88 uterine cervical cancers. Correlation between expression and prognostic variables and the survival was examined. METHODS: Eighty-eight patients with stage IB disease, treated primarily with surgery, were examined histopathologically and immunohistochemically. CD44v6 expressions of tumoral tissue and the nonneoplastic tissue nearby were examined using antiCD44v6 monoclonal antibody. CD44v6 expression was compared to the known clinicopathologic prognostic variables and survival of patients. RESULTS: Nonneoplastic epithelium of the sections showed CD44v6 expression predominantly in basal and parabasal layers at least in traces. CD44v6 overexpression in neoplastic islands was evaluated as "general," "basal" (only in the basal portion of neoplastic islands), and "nonbasal" (also in the central portion of the neoplastic islands) separately. When expression and prognostic variables were compared, CD44v6 non-basal expression was found to be significant in nonsquamous cancers, when the tumor diameter was greater than 3 cm and in the tumors that showed recurrences. Univariate survival analysis with the Kaplan-Meier method showed that only the age of the patient is significantly correlated with disease-free survival. Interestingly when the same analysis was done for 5-year overall survival, diameter of the primary tumor, depth of cervical stromal invasion, existence and number of lymph node involvement, positivity for general CD44v6 expression, and positivity for nonbasal expression were found to be statistically significant. Furthermore multivariate analysis with Cox regression showed that nonbasal CD44v6 expression and lymph node involvement are independent variables for 5-year overall survival. CONCLUSION: These results indicate that CD44v6 expression is associated with some of the important clinicopathologic prognostic variables and appears to be a predictor of advanced pathological-surgical stage of early clinical stage cervical carcinoma. CD44v6 nonbasal expression is significantly correlated with overall survival.     

Expression of the c-Met in advanced epithelial ovarian cancer and its prognostic significance

The purpose of this study was to evaluate the prognostic significance of c-Met expression in advanced cases of epithelial ovarian carcinoma. Paraffin-embedded tissues from 41 stage IIIC primary ovarian adenocarcinoma were stained immunohistochemically for c-Met expression. The expression of c-Met was correlated with conventional clinicopathologic parameters and with overall survival of the patients. c-Met expression was found in 60.9% of cases. This clinicopathologic study showed that epithelial ovarian carcinomas with c-Met expression had higher histologic tumor grade and were more frequently associated with para-aortic lymph node metastasis (P < 0.05). In multivariate analysis, c-Met expression remained as a statistically significant predictor for survival with histologic grade. The patients with stage IIIC epithelial ovarian cancers whose tumors expressed c-Met were more likely to have high-grade tumors, have more para-aortic lymph node involvement, and have a significantly worse overall survival than those whose tumors were c-Met negative. In conclusion, c-Met expression might be a potential prognostic marker for patients with advanced-stage epithelial ovarian cancers.     

F-18 fluorodeoxyglucose uptake in primary cervical cancer as an indicator of prognosis after radiation therapy

PURPOSE: We evaluated the prognostic significance of tumor metabolic activity on pretreatment positron emission tomography using the glucose analog F-18 fluorodeoxyglucose (FDG-PET) in patients with carcinoma of the cervix undergoing radiotherapy with or without concurrent chemotherapy. METHODS: We studied 96 consecutive patients who underwent FDG-PET prior to initiation of radiotherapy with or without concurrent chemotherapy for carcinoma of the cervix. Pretreatment FDG uptake of the primary tumor was assessed with the semiquantitative standardized uptake value (SUV) and correlated with disease-free and overall survival. Survival was estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed with the logistic likelihood ratio test and the Cox proportional hazards model, respectively. RESULTS.: Five-year disease-free survivals in patients with maximal SUV <10.2 and > or =10.2 were 71% and 52% (P = 0.0289) respectively, while overall survivals were 72% and 69% (P = 0.4), respectively. On multivariate analysis, lymph node metastasis on FDG-PET was found to be predictive of disease-free survival (P < 0.0001). Both the SUV for FDG and FIGO Stage I disease were found to be marginally predictive of disease-free survival (P = 0.055 and P = 0.058, respectively). CONCLUSIONS: FDG uptake within primary cervical cancer, as measured by SUV, is predictive of disease-free survival in patients undergoing radiotherapy for cervical cancer. High FDG uptake may be useful in identifying patients who may require more aggressive initial therapy.     

Adenosquamous carcinoma of the cervix: prognosis in stage IB

The outcome of women with adenosquamous carcinoma of the cervix has been a controversial issue. To assess the prognostic significance of this cell type, the medical records of 29 patients with stage IB primary adenosquamous carcinoma of the cervix were reviewed. Twenty-six had cervical tumors measuring 3 cm or less. With a median follow-up of 60 months, the overall disease-free 5-year survival was 85%. Pelvic lymph node metastases were found in three of 19 patients (16%) with stage IB, and periaortic lymph nodes were negative in eight. A log-likelihood chi 2 test comparing lymphatic spread, recurrence rate, and 5-year disease-free survival in patients with stage IB disease and tumors less than 3 cm versus a similar group of 58 patients with pure squamous cell carcinoma of equivalent stage and comparable size treated during the same time disclosed no significant differences in any of the indicators analyzed. We conclude that stage IB adenosquamous carcinoma of the cervix does not differ in its metastatic potential or outcome from the more common pure squamous cell carcinoma.     

A comparison of prognoses of pathologic stage Ib adenocarcinoma and squamous cell carcinoma of the uterine cervix

OBJECTIVES: The influence of the histology of adenocarcinoma on recurrence and survival for patients treated with radical hysterectomy and diagnosed as having pathologic stage Ib cervical cancer was investigated. METHODS: Five hundred and nine patients (405 squamous cell carcinomas, 104 adenocarcinomas) with pathologic stage Ib cervical cancer treated initially at the Aichi Cancer Center between 1976 and 1995 were studied. RESULTS: Multivariate analysis identified the prognostic variables as histology of adenocarcinoma, number of lymph nodes involved, and tumor size beyond 4 cm. Five-year overall survival and disease-free survival of patients with adenocarcinoma in the presence of lymph node metastasis were 63.2 and 47.4%, respectively, significantly poorer than for squamous cell carcinoma (83.6 and 80.6%; P < 0.001 and P = 0.002, respectively). These were not different in the absence of lymph node metastasis (adenocarcinoma, 93.9 and 92.7%; squamous cell carcinoma, 97.9% and 96.1%; P = 0.067 and P = 0.250, respectively). CONCLUSIONS: The independent significant risk factors for the recurrence and survival of pathologic stage Ib cervical cancer were the presence of lymph node metastasis, large tumor size beyond 4 cm, and histology of adenocarcinoma. The prognosis of patients with adenocarcinoma was poorer than of patients with squamous cell carcinoma in the presence of lymph node metastasis, while the prognosis of pathologic stage Ib cervical cancer was equivalent when there was no metastasis.     

Loss of cell-surface heparan sulfate expression in both cervical intraepithelial neoplasm and invasive cervical cancer

OBJECTIVE: Syndecan-1 binds to various extracellular matrix components via its heparan sulfate glycosaminoglycans (HS-GAG) and most of its biological functions are considered to be associated with this process. The aims of this study are to investigate its expression in cervical neoplasms. METHODS: We investigated the expression of both the syndecan-1 core protein and cell-surface HS-GAG by immunohistochemistry in 53 cervical intraepithelial neoplasm (CIN), 19 microinvasive, 143 invasive cervical cancers, and 29 metastatic lymph node samples, and analyzed correlations with various clinicopathological features. RESULTS: The progression of CIN to early invasive cancer was found to associate with reduced levels of both syndecan-1 and HS-GAG expression. In squamous cell carcinomas, HS-GAG expression was significantly lower in cases with lymph-vascular space invasion. Additionally, the overall survival rates for patients exhibiting low HS-GAG expression was significantly lower than patients exhibiting high HS-GAG expression (P = 0.019). Low HS-GAG expression in positive nodes was determined to be a disease-free and overall survival prognostic factor (P = 0.028 and P = 0.018, respectively). CONCLUSION:The loss of syndecan-1 and HS-GAG expression is an early event in cervical carcinogenesis. The loss of HS-GAG expression particularly in positive nodes can serve as an indicator of aggressive disease potential and poor prognosis in patients with invasive cervical cancer.     

Prognostic factors in pathologic parametrium-positive patients with stage IB-IIB cervical cancer treated by radical surgery and adjuvant therapy

OBJECTIVE: The purpose of the present study was to identify prognostic factors and recurrent patterns in pathologic parametrium-positive patients with stage IB-IIB cervical cancers treated by radical surgery and adjuvant therapy. METHODS: The patient population consisted of 84 individuals presenting with stage IB-IIB cervical cancers and histologically proven parametrial invasion. All these patients were treated postoperatively with adjuvant external whole pelvic irradiation, combination chemotherapy, or chemoradiotherapy. RESULTS: The 5-year disease-free survival rate was found to be 67.2% and 5-year overall survival rate, 75.4%. Multivariate analysis revealed that vaginal invasion (p=0.0008), lymph node metastasis (p=0.002), and non-squamous histology (p=0.010) were independent indicators of the disease-free survival rates and that the vaginal invasion (p=0.009) and lymph node metastasis (p=0.011) were independent prognostic factors for the overall survival rates. The 5-year overall survival rate was approximately 90% for patients without these risk factors. Disease recurrence was observed in 26 patients (31.0%) with a median time of 16.5 months (range, 5-59 months) from the surgery. Hematogenous recurrences, including those in the lung, liver, and bone, were significantly higher in patients with non-squamous cell carcinomas (p=0.008). Distant lymph node recurrences were significantly higher in patients with positive pelvic lymph node and vaginal invasion (p=0.004 and p=0.023, respectively). Pelvic recurrences were significantly higher in patients with vaginal invasion (p=0.026). CONCLUSIONS: Vaginal invasion and lymph node metastasis are independent indicators for disease-free and overall survival rates in pathologic parametrium-positive patients with stage IB-IIB cervical cancer treated by radical surgery and adjuvant therapy. The survival rate is excellent in the patients without these risk factors. Hematogenous recurrence may be evident in patients with non-squamous cell carcinomas.     

Prognostic factors of adenocarcinoma of the uterine cervix

OBJECTIVE: The prognostic importance of adenocarcinoma of the uterine cervix was investigated. Methods. One hundred ninety-three patients (144 had stage I disease, 41 stage II, and 8 stage III-IV) with invasive adenocarcinoma of the uterine cervix treated initially at the Aichi Cancer Center between 1964 and 1995 were studied. RESULTS: Of all the invasive cervical cancers, 8.8% were adenocarcinomas that had been increasing during the past decade. The overall 5-year survival for stage I was 88.8%, stage II 44.9%, and stage III-IV 0% In univariate analysis, the clinicopathological factors associated with overall survival and disease-free survival were age of patient, stage of disease, presence of nodal metastasis, number of lymph nodes involved, lymph-vascular space invasion, tumor size, and intraperitoneal metastasis. Multivariate analysis performed in all cases identified the clinical stage of disease, the presence of nodal metastasis, number of lymph nodes involved, lymph-vascular space invasion, and tumor size as the independent risk factors for recurrence and survival. In the analysis of stage I disease, lymph node metastasis and tumor size were the significant prognostic factors, while lymph-vascular space invasion and tumor size were the factors in advanced disease. Tumor grade and histological type were not associated with recurrence and survival. CONCLUSION: These results suggested the association of lymph node metastasis with the prognosis of early stage adenocarcinoma of the uterine cervix and lymph-vascular space invasion with the advanced stage. Tumor size was an independent risk factor throughout all stages.     

宫颈小细胞癌与非小细胞癌临床特征及预后的对比研究

目的:对比性研究宫颈小细胞癌(SCCC)与宫颈非小细胞癌在发病特点、临床特征、治疗方案、预后情况等方面的差异,并探究影响其预后的因素。方法:回顾性分析2003年5月至2015年6月四川大学华西第二医院收治的宫颈小细胞癌患者63例(SCCC组)和根据诊断时间及相近的FIGO分期配对的宫颈非小细胞癌(鳞癌、腺癌)患者60例(对照组)的临床病理资料及生存情况,采用Pearson卡方检验或Fisher确切概率法比较两组临床特征、治疗方案等方面的差异,Kaplan-Meier方法比较两组总体生存率及无病生存率的差异,单因素和多因素分析影响SCCC预后的因素。结果:(1)SCCC组患者初诊的中位年龄较对照组年轻(40岁vs 44岁,P=0.001),淋巴结转移率、宫旁浸润率、脉管累及率及手术切缘阳性率也均显著高于对照组(P0.05)。而在临床症状、肿块大小、诊断分期、术前治疗、术后治疗等方面比较两者差异均无统计学意义(P0.05)。(2)生存分析中,SCCC组的累积5年生存率(29.2%)与累积5年无瘤生存率(26.6%),显著低于对照组(分别为82.6%、76.7%),差异有统计学意义(P0.05)。(3)在影响SCCC预后的多因素COX多元回归分析结果显示,有淋巴结转移是影响患者5年总生存率和5年无瘤生存率的独立危险因素(HR=4.784、3.067,P0.05)。肿块直径≥4 cm是影响5年总生存率的独立危险因素(HR=3.610,P0.05)和FIGO分期(ⅠB2以上)是影响无瘤生存率的独立危险因素(HR=2.793,P0.05)。结论:SCCC患者更年轻,其临床症状、病灶外观、治疗方案等和宫颈非小细胞癌相似,但淋巴结转移率、脉管累及率、宫旁浸润率及手术切缘阳性率均显著高于宫颈非小细胞癌,预后极差。影响SCCC患者预后的主要因素为有无淋巴结转移、FIGO分期、肿块直径。     

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. METHODS: A 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. RESULTS: Age, 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 > 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. CONCLUSION: Prognosis 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.     

Prognostic factors in FIGO stage IB cervical cancer without lymph node metastasis and the role of adjuvant radiotherapy after radical hysterectomy

OBJECTIVES: The aim of this study was to evaluate the clinical and pathologic prognostic variables for disease free survival, overall survival and the role of adjuvant radiotherapy in FIGO stage IB cervical carcinoma without lymph node metastasis. METHODS: A retrospective review was performed of 393 patients with lymph node negative stage IB cervical cancer treated by type 3 hysterectomy and pelvic lymphadenectomy at the Hacettepe University Hospitals between 1980 and 1997. RESULTS: The disease free survival and overall survival were 87.6 and 91.0%, respectively. In univariate analysis, tumor size, depth of invasion, vaginal involvement, lympho-vascular space involvement (LVSI) and adjuvant radiotherapy were found significant in disease free survival. Overall survival was affected by tumor size, LVSI, vaginal involvement and adjuvant radiotherapy. Tumor size, LVSI and vaginal involvement were found as independent prognostic factors for overall and disease free survival in multivariate analysis. Disease free survival, recurrence rate and site did not differ between patients underwent radical surgery and radical surgery plus radiotherapy. CONCLUSION: Tumor size, LVSI and vaginal involvement were independent prognostic factors in lymph node negative FIGO stage IB cervical cancer. Adjuvant radiotherapy in stage IB cervical cancer patients with negative nodes provides no survival advantage or better local tumoral control.     

局部晚期宫颈癌100例淋巴结转移特点及临床分析

目的：探索局部晚期（ⅠB2/ⅡA2期）宫颈癌的淋巴结转移特点及新辅助化疗对预后及并发症发生率的影响。方法：回顾性分析2008年1月-2016年12月南京医科大学第一附属医院收治的424例ⅠA2～ⅡA2期宫颈鳞癌或腺癌患者的临床资料,随访每位患者的生存情况,比较局部晚期宫颈癌患者淋巴结转移情况及新辅助化疗和直接手术患者在手术并发症及预后方面的差异。结果：共424例宫颈癌患者纳入研究,100例局部晚期宫颈癌患者中有68例直接行根治性手术治疗,32例先行1～2次介入或静脉新辅助化疗后行宫颈癌根治术,术后病理提示盆腔淋巴结转移者20例,没有发现腹主动脉旁淋巴结转移。单因素分析提示深肌层浸润、淋巴脉管间隙浸润（lymph vascular space invasion,LVSI）与淋巴结转移相关（P＜0.05）;组织学类型、分化程度、是否行新辅助化疗与淋巴结转移无关（P＞0.05）。将有统计学意义的单因素进行Logistic回归分析显示,LVSI为淋巴结转移的独立危险因素（P＜0.05）。新辅助化疗组淋巴结转移率为22.2％,手术组则为17.2％,2组比较差异无统计学意义（P＞0.05）。总生存期及无瘤生存期方面,局部晚期宫颈癌明显低于早期者。新辅助化疗组的术后感染发生率较低,手术时间和腹腔引流管留置时间较短,但2组差异无统计学意义（P＞0.05）,而术中输尿管支架置入率、输血率、其他相邻脏器损伤的发生率2组相似。结论：局部晚期宫颈癌预后较早期差,淋巴结转移率明显高于早期,盆腔淋巴结转移主要与LVSI及深肌层浸润有关。新辅助化疗对局部晚期宫颈癌的影响尚不明确,也没有证据证明新辅助化疗影响盆腔淋巴结转移的检出率,在手术相关并发症的发生率方面还需更大样本或多中心的研究。     

Long-term survival and sequelae after surgical management of invasive cervical carcinoma diagnosed at the time of simple hysterectomy.

From 1956 to 1988, 27 women (median age, 60 years) found to have occult invasive carcinoma of the cervix at total hysterectomy underwent radical reoperation consisting of radical parametriectomy, upper vaginectomy, and pelvic lymphadenectomy. Residual disease was present at reexploration in 4 (15%) of the 27 patients: in the pelvic lymph nodes in 2, in the parametrium in 1, and in the vagina and a para-aortic node in 1. All patients were followed a minimum of 18 months; there were no deaths within 3 months of operation. However, 2 (7%) of the 27 patients developed ureterovaginal fistulas. Recurrent disease was observed in 6 (22%) of the patients: 2 had successful salvage procedures, and 4 died of disease, all within 4 years of reoperation. Recurrence correlated with the presence of residual disease at reoperation and with nonsquamous histologic findings. At a median follow-up of 8.4 years, 23 of the 27 patients were alive and disease-free. The 5-year absolute survival estimate (Kaplan-Meier) was 82%. Radical reoperation can be performed safely in selected patients who have early-stage invasive carcinoma of the cervix at the time of total hysterectomy with the expectation of an acceptable rate of long-term disease-free survival.     

Can initial serum cyfra 21-1, SCC antigen, and TPA levels in squamous cell cervical cancer predict lymph node metastases or prognosis?

OBJECTIVE: The aim of this study was to determine whether lymph node metastases or prognosis can be predicted by initial serum Cyfra 21-1, tissue polypeptide antigen (TPA), and squamous cell carcinoma antigen (SCC-Ag) levels in squamous cell cervical cancer. METHODS: Pretreatment serum levels of 92 patients were correlated with clinicopathologic parameters and prognostic data. The clinical performance of the tests was evaluated by their receiver operating characteristic curves. The prognostic power of the variables was assessed using Cox regression analysis. RESULTS: Serum levels of each marker were significantly related to tumor stage, size, and depth of infiltration. The clinical performance of each marker in predicting lymph node metastases or parametrial involvement was poor. In the stepwise Cox regression analysis, regarding patients with early stage cervical cancer (stage Ib/IIa, n = 63), tumor size (P = 0.0005) was the only independent prognostic factor for disease-free interval. Lymph node status (P = 0.0014), tumor size (P = 0.004), and parametrial involvement (P = 0.025) were independent risk factors for survival. Considering all patients with stages Ia through IVb disease, tumor size (P = 0.0001) and TPA level (P = 0. 026) were independent risk factors for disease-free interval, whereas tumor size (P = 0.0001) and parametrial involvement (P = 0. 0002) were risk factors for survival. CONCLUSIONS: Pretreatment Cyfra 21-1, TPA, and SCC-Ag levels were strongly related to tumor burden, but insufficiently reliable for identifying patients at risk of the presence of lymph node metastases or parametrial involvement. Serum levels of each marker showed no independent prognostic value in early stage cervical cancer.     

Association between RCAS1 expression and microenvironmental immune cell death in uterine cervical cancer

OBJECTIVE.: The presence of regional lymph node metastasis is one of the prognostic factors for uterine cervical cancer. The development of metastasis requires that cancer cells avoid lymphocyte attack. Impaired lymphocyte function is mediated by apoptotic factors including receptor-binding cancer antigen expressed on SiSo cells (RCAS1), Fas ligand (FasL), and tumor necrosis factor-alpha (TNF-alpha). Our aim was to evaluate the association between expression of these factors and microenvironmental lymphocyte apoptosis in this disease. METHODS.: Immunohistochemical methods were used to determine the relationship between the expression of RCAS1, FasL, and TNF-alpha, and the number of apoptotic lymphocytes in primary lesions and metastatic lymph nodes in patients with cervical cancer. RESULTS.: Expression of these apoptosis-inducing molecules was quite different in primary tumors and metastatic lymph nodes: RCAS1 expression in lymph nodes was significantly higher than that in primary lesions (P < 0.0001), whereas FasL and TNF-alpha expressions at these two locations were not significantly different. The number of cells with positive expression of RCAS1, but not of FasL or TNF-alpha, was significantly correlated with the number of apoptotic lymphocytes in uterine cervix and metastatic lymph nodes (P < 0.0001 for both). CONCLUSION.: RCAS1 expression may be related to tumor cell evasion of immune surveillance via induction of lymphocyte apoptosis in primary lesions and metastatic lymph nodes in uterine cervical cancer.     

Survival of 231 cervical cancer patients, treated by radical hysterectomy, according to clinical and histopathological features

PURPOSE OF INVESTIGATION: The purpose of the study was to estimate the five-year survival of cervical cancer patients after radical hysterectomy, taking into account clinical data and histopathological parameters. METHODS: 231 patients with invasive cervical carcinoma were diagnosed, surgically treated--Piver III--and followed-up. Histological examination of specimens was performed according to the British NHS-CSP guidelines. RESULTS: We discovered no statistical significance as regards age at diagnosis, age at menarche and menopause, and number of pregnancies, deliveries and abortions, in relation to survival. We concluded that the clinical stage according to FIGO classification influenced survival. Statistical significances were: Ia2 vs Ib, Ib vs IIa and IIa vs more advanced than IIa. The following histopathological parameters correlated with survival: depth of cervical invasion, primary lesion volume, and parametrial, uterine, vaginal and lymph node involvement. Using Cox's proportional hazards model we found that only lymph node status and FIGO staging were independent parameters correlating with survival and mortality risk in our study. CONCLUSION: Prognostic indexes classifying patients at specific disease stages into different categories of risk should be based on histopathological features listed above. Such indexes are yet to be validated in larger, prospective studies conducted in different patient populations.     

子宫颈癌伴盆腔淋巴结转移患者的复发及预后分析

目的 探讨宫颈癌伴盆腔淋巴结转移患者的复发规律及预后影响因素.方法 选取1994年1月至2001年12月问中山大学肿瘤防治中心收治的按国际妇产科联盟(FIGO)的标准其临床分期为I b1～II a期的宫颈癌伴盆腔淋巴结转移的患者共124例,结合临床病理资料对其复发及预后情况进行回顾性分析.结果 患者的5年总生存率和5年无瘤生存率分别为63.3%、61.4%;总复发率为39.5%(49/124),其中复发部位明确的41例患者(盆腔内、盆腔外和盆腔内外同时复发患者分别为25、13和3例)中盆腔内复发率(61.O%,25/41)显著高于盆腔外复发率(31.7%,13/41;P=0.008).多因素分析显示,髂总淋巴结转移是影响患者预后的独立的危险因素(P=0.035).根据这一因素,将盆腔淋巴结转移的患者分为低危组(髂总淋巴结无转移,104例)和高危组(髂总淋巴结转移,20例),其5年无瘤生存率分别为69.4%和24.5%,两组比较,差异有统计学意义(P=0.003);低危组盆腔内复发率为22.1%(23/104),高危组为25.0%(5/20),两组比较,差异无统计学意义(P>0.05);低危组盆腔外复发率为7.7%(8/104),高危组为40.O%(8/20),两组比较,差异有统计学意义(P<0.01).结论 伴盆腔淋巴结转移的宫颈癌患者以盆腔内复发为主,而其中髂总淋巴结转移者以盆腔外复发为主.髂总淋巴结转移是影响宫颈癌患者预后的独立的危险因素.     

Pretreatment tumor diameter/volume and pelvic lymph node status assessed by magnetic resonance imaging for uterine cervical carcinoma treated with concurrent chemotherapy and radiotherapy

Aim:  The aim is to evaluate the prognostic value of tumor diameter, volume and pelvic lymph node status assessed by magnetic resonance imaging (MRI) in patients with uterine cervical carcinoma patients treated with concurrent chemotherapy and radiotherapy.
Methods:  Ninety-eight patients diagnosed with stage IB to IIIB cervical carcinoma were entered into the study. Tumor diameter was evaluated in T2-weighted image. The tumor volume was calculated by the equation (volume = width × length × height × π/6) as an ellipsoid approximation. Univariate and multivariate analyses were performed to identify the prognostic factors for overall survival (OS), disease-free survival (DFS), pelvic control (PC) and distant metastasis-free survival (DMFS).
Results:  The 5-year OS, DFS, PC and DMFS rate were 59.8%, 57.3%, 67.9% and 78.8%, respectively. Using univariate analyses, large MRI tumor diameter (≥4 cm), large tumor volume (≥30 mL), pelvic enlarged pelvic lymph nodes, large clinical diameter (≥4 cm) and International Federation of Gynecology and Obstetrics (FigO) stage showed a statistically significantly unfavorable influence on OS and DFS. In multivariate analyses, large tumor volume affected OS, DFS, PC and DMFS, and enlarged pelvic lymph nodes also affected OS.
Conclusion:  Tumor volume and enlarged pelvic lymph nodes determined by pretreatment MRI examinations were significant prognostic factors for patients with invasive cervical carcinoma treated with concurrent chemotherapy and radiotherapy.     

Epidermal Growth Factor Receptor in Vulvar Malignancies and Its Relationship to Metastasis and Patient Survival

Objective.To evaluate the level of epidermal growth factor receptor (EGF-R) expression in vulvar malignancies and to determine if a correlation exists between EGF-R levels and metastasis or patient survival.Methods.All patients with a diagnosis of invasive squamous cell carcinoma of the vulva who were treated at our institution with a primary radical vulvectomy and inguinal lymph node dissection from 1983 to 1993 were eligible for the study. Sixty-one patients with available tissue blocks of benign vulvar epithelium, the primary malignant vulvar lesion, and groin node metastasis (when positive) were included in the study. Semiquantitative EGF-R expression was determined in a blinded fashion utilizing immunohistochemical staining of appropriate tissue samples. Survival was calculated utilizing Kaplan–Meier life table analysis based upon disease-free survival.Results.A significant increase (P< 0.001) in mean EGF-R levels was demonstrated in the primary tumor (67%) versus benign vulvar epithelium (31%). In the 14 patients with lymph node metastasis, the mean EGF-R level in the primary tumor was 65% versus 88% in the metastatic lesion (P< 0.001). The likelihood of lymph node metastasis was elevated in those patients with a benign tissue EGF-R level ≥40% (P< 0.03) and in those patients with a primary tumor EGF-R level ≥90% (P< 0.025). Life table analysis revealed a cumulative disease-free survival of 45% for all patients. Disease-free survival in those patients with EGF-R levels ≥90% in the primary tumor was 25%, contrasting with a disease-free survival of 54% in those patients with EGF-R levels <90% (P< 0.05).Conclusions.There is a progressive increase in EGF-R expression from benign vulvar epithelium to primary malignant tissue to metastatic lesions within the same patient. Increased expression of EGF-R in the primary vulvar malignancy is significantly associated with lymph node metastasis and decreased patient survival. Increased expression of EGF-R in histologically benign vulvar epithelium has a significant association with lymph node metastasis and may predict decreased patient survival.     

Expression of indoleamine 2,3-dioxygenase predicts shorter survival in patients with vulvar squamous cell carcinoma (vSCC) not influencing on the recruitment of FOXP3-expressing regulatory T cells in cancer nests

Objective

Regulatory T cells (Tregs), and the enzyme indoleamine 2,3-dioxygenase (IDO), have potential regulatory properties for immune escape in cancer. Inhibitors of IDO are available and could potentially be used in vulvar cancer if IDO was proved to drive progression of the disease. The aim of this study was to evaluate the expression of factor forkhead boxP3 (FOXP3), a marker of Tregs, and IDO in vulvar squamous cell carcinoma (vSCC), and to verify their prognostic significance.

Methods

76 primary tumors and 35 lymph node metastases derived from 76 patients with full clinical history were analyzed. The intratumoral infiltration of Tregs and IDO expression within cancer were evaluated by immunohistochemistry.

Results

The number of Tregs in primary tumor and in corresponding lymph node metastasis was significantly correlated. Intensity of Treg infiltrates in the primary and metastatic sites was not correlated to IDO expression and had no influence on the overall patient survival. High IDO expression was associated with significantly worse overall survival among vSCC patients and was found to be an independent prognostic factor similarly to the tumor grade and patient's age.

Conclusions

The degree of intratumoral Treg infiltrates is an individual feature and remains stable throughout the course of the disease without impact on the patient's survival. IDO expression predicts shorter survival of vSCC patients. If immunologic tolerance of the tumor is promoted by the overexpression of IDO it will not influence the number of intratumoral Tregs. IDO expression seems to be an independent prognostic factor in patients with vSCC.