Squamous cell carcinoma antigen serum levels as prognostic parameter in patients with early stage vulvar cancer

OBJECTIVE: To determine whether SCC-Ag serum levels can be used as a prognostic parameter in surgically treated early stage vulvar cancer. METHODS: SCC-Ag serum levels were measured preoperatively in 61 surgically staged patients with squamous cell vulvar cancer (UICC pT1 and pT2). Results were correlated to clinical data. RESULTS: Mean (standard deviation) SCC-Ag serum levels in patients with vulvar cancer were 1.5 (1.99) ng/mL. SCC-Ag serum levels were significantly higher in patients with pT2 vulvar cancer (2.2 [2.6] ng/mL) compared with patients with pT1 vulvar cancer (1.0 [1.2] ng/mL, P = 0.034). SCC-Ag serum levels were not associated with lymph node involvement (P = 0.1), tumor grade (P = 0.6), and patients' age (P = 0.5). Multivariate Cox regression models considering tumor stage, lymph node involvement, patients' age, and SCC-Ag serum levels as covariates showed that lymph node involvement (P = 0.04 and P = 0.01) and tumor stage (P = 0.006 and P = 0.009), but not SCC-Ag serum levels (P = 0.8 and P = 0.6), and patients' age (P = 0.08 and P = 0.22) are prognostic factors for disease-free and overall survival, respectively. CONCLUSION: SCC-Ag serum levels cannot be used as an additional prognostic parameter in patients with surgically treated early stage vulvar cancer.     

Squamous cell carcinoma antigen in cervical cancer.

Squamous cell carcinoma (SCC) antigen was described as being associated with malignant disease of the uterine cervix, and was determined by a radioimmunoassay technique. We studied squamous cell carcinoma serum levels in 72 patients from our gynecological clinic. Forty-three were diagnosed as having gynecological malignancies, and 29 as having benign diseases. The malignant disease group included 35 carcinomas of the uterine cervix, 7 endometrial cancers, and 3 vulvar cancers. Gynecological cancers were classified according to the FIGO system. We also determined SCC levels among 69 healthy subjects. Results showed that 97.1% of healthy subjects were below the cut-off point, 2.5 micrograms/l. Patients with benign gynecological diseases had increased SCC levels in 5.9% of cases. Among gynecological cancers, 56% of 23 cases of cervical cancer and one of three vulvar cancer, all of them in the active phase, had increased levels. The nine squamous carcinomas of the cervix with no evidence of disease, as well as seven endometrial adenocarcinomas with active disease were negative. Thirty-three percent of 12 cervical cancers in Stages I and II were high levels, compared to 81% of 11 advanced stages; none of the 2 early stage carcinoma of the vulva, but 1 advanced stage were increased. SCC is clinically applicable to monitor size and tumor volume of carcinomas of the uterine cervix derived from squamous epithelium.     

Use of squamous cell carcinoma antigen as a biomarker of chemotherapy response in patients with metastatic cervical carcinoma

Objective

To examine the use of squamous cell carcinoma antigen (SCCA) as a biomarker of chemotherapy response in patients who underwent chemotherapy for metastatic cervical carcinoma.

Study design

The study population consisted of patients who underwent first-line chemotherapy for metastatic cervical carcinoma between 1999 and 2009. SCCA levels were serially measured before, during and after chemotherapy. Radiographic responses were evaluated according to the criteria of the World Health Organization. A logistic model was used to determine the best prediction model, and internal and external validation of the prediction model were performed to compare the areas under the receiver operating characteristic curves (AUCs).

Results

In total, 55 patients were included in the analysis. Data for 32 patients enrolled in various clinical trials were used to develop the prediction model. Patients who achieved a radiographic response showed a significant decline in SCCA levels between the second and third cycles of chemotherapy, whereas patients who did not achieve a radiographic response showed constant SCCA levels over the same period. The prediction model was developed on the basis of changes in the SCCA level between the second and third cycles of chemotherapy (AUC = 0.832) and the baseline SCCA level. The AUC after external validation, calculated using the data of the clinical practice population (n = 22), was 0.871.

Conclusions

A response to chemotherapy was possible for patients in whom SCCA levels declined between the second and third cycles of chemotherapy.     

Squamous cell carcinoma of the vulva: prognostic factors influencing survival.

One hundred seventy-two cases of patients with squamous cell cancer of the vulva treated at the University of Michigan Medical Center from 1975 to 1988 are reported. The mean age was 66 years with a range of 21 to 101 years. The distribution by stage included Stage I, 65; Stage II, 44; Stage III, 50; and Stage IV, 13 patients. Groin node dissections performed on 145 patients showed negative nodes, 58%; unilateral positive nodes, 28%; and bilateral positive nodes, 14%. The distribution of patients with positive nodes was influenced by stage: Stage I, 14%; Stage II, 23%; Stage III, 72%; Stage IV, 92%. The overall cumulative 5-year survival was 71% and this was significantly influenced by stage of disease: Stage I, 94%; Stage II, 91%; Stage III, 36%; Stage IV, 26%. Stages I/II and III/IV were combined for analysis. In Stages I/II, survival was significantly influenced by tumor grade while size, patient age, and lymph node status did not influence survival. In Stage III/IV, survival was significantly influenced by tumor size, node status, and number of positive nodes while grade, patient age, and tumor location did not influence survival. Squamous cell cancer of the vulva is effectively treated with radical surgery but advanced-stage disease with regional metastases significantly alters survival.     

Squamous cell carcinoma antigen: pretreatment levels as an indicator of advanced or metastatic disease

Pretreatment values of squamous cell carcinoma antigen (SCC) were obtained in 100 consecutive patients with squamous cell carcinoma of the cervix presenting to the Regional Gynaecological Oncology Centre in Gateshead, UK. Nine patients deemed to have locally advanced disease not suitable for primary surgery had elevated levels. Ninety-one patients were suitable for primary surgery. Sixty-seven had normal SCC levels, two of which had lymph node metastases. Twenty-four had elevated SCC levels, 14 of which had lymph node metastases. Two early recurrences have been detected in the raised SCC group where no lymph node metastases were present. Elevated levels of SCC in the pretreatment assessment indicate a high risk of lymph node metastases and of developing recurrent disease after primary surgery.     

Value of squamous cell carcinoma antigen levels in invasive cervical carcinoma

Squamous cell carcinoma (SCC) antigen (Ag) levels were measured by radioimmunoassay in 64 patients with invasive squamous cell cervical carcinoma and 9 patients with nonsquamous carcinoma before the initiation of treatment. The mean antigen level in the squamous group was 10.5 ng/ml compared with 1.3 ng/ml in the nonsquamous group. In the patients with squamous cell carcinoma, mean SCC Ag level correlated well with stage, except for bulky stage IB tumors (P less than 0.05), where mean level was much higher than expected. Patients with exophytic tumors had significantly higher SCC Ag levels than those with nonexophytic tumors. Follow-up on 62 evaluable patients ranged from 20 to 40 months. The mean pretreatment SCC Ag level for patients free of disease at last contact was 5.6 ng/ml, in contrast to 16.1 ng/ml for those with recurrent disease. Only 32% of patients free of disease had pretreatment levels of 4.0 ng/ml or greater, while 86% of those with recurrent disease had such values (P less than 0.05). Forty patients had follow-up samples drawn 1 to 14 months after treatment. Mean post-treatment SCC Ag levels dropped to 1.8 ng/ml in 21 patients free of disease (73% decrease), but remained elevated at 13.4 ng/ml (17% decrease) in 19 patients with recurrences. The specificity of follow-up SCC Ag levels as a predictive test for outcome was 90%, with a sensitivity of 63%. We conclude that pretreatment SCC Ag levels correlate well with tumor stage, lesion morphology, and extent of disease. SCC antigen levels may be used to follow patients to determine effectiveness of treatment.     

Squamous cell cancer of the cervix: prognostic factors related to survival

Seven hundred and fifty-three patients with invasive squamous cell cancer of the cervix treated at the University of Michigan from 1970–1985 are reported. These included stage IA 43, stage IB 345, stage IIA 27, stage IIB 163, stage IIIA 4, stage IIIB 113, stage IVA 32, stage IVB 26. The age ranged from 18 to 92 years with a mean of 49.9 years. Clinical characteristics included: nulliparity 11%, married 93%, obese 41%, hypertensive 37%, diabetes 10%, smoking 50%, bleeding 76%. The cumulative five-year survival for all patients was 67% and this was influenced by the stage of disease: stage IA 98%, stage IB 89%, stage IIA 72%, stage IIB 62%, stage III 37%, stage IVA 14%, stage IVB 4%. Patients with a well-differentiated tumor had an 85% survival rate while those with a poorly differentiated tumor had a 57% survival rate. The probability of metastatic disease to lymph nodes corresponded to the stage of disease; stage I 17%, stage II 55%, stage III 70%, stage IV 81%. When lymph nodes were negative, the survival rate for all patients was 86% while those with positive nodes had a 33% survival rate. Factors which influenced survival in the univariate analysis included stage, node status, tumor grade, age, interval from previous pelvic examination, diabetes. Only stage, node status and tumor grade maintained significance in the multiple proportion hazard analysis.     

Squamous cell carcinoma (SCC) antigen in patients with invasive cervical carcinoma during primary irradiation

In a prospective study, serum concentrations of squamous cell carcinoma (SCC) antigen were determined by radioimmunoassay from 74 healthy volunteers and 54 patients with cervical carcinoma who underwent irradiation therapy. 5.4% of the controls had SCC levels greater than 3.0 ng/ml, which was considered as upper limit of the normal range. 31/54 (57.4%) patients and 60% of the patients with SCC had elevated pretreatment levels. In all patients with pretreatment serum levels above 3.0 ng/ml, SCC serum levels decreased during irradiation therapy. 4/5 patients with posttreatment levels greater than 0.5 ng/ml developed recurrence or persistence of tumor, 1 patient could not be followed up. Good conformity was found between SCC antigen serum levels and therapy response. SCC antigen determinations during and after therapy provide a useful tool in detecting progression and persistence of tumor.     

The clinical values of squamous cell carcinoma antigen and carcinoembryonic antigen in patients with cervical cancer treated with concurrent chemoradiotherapy

The objective of this study was to determine the prognostic significance of the pre- and posttreatment serum levels of the squamous cell carcinoma antigen (SCC-Ag) and carcinoembryonic antigen (CEA). From 2001 to 2005, 211 patients were treated with concurrent chemoradiotherapy (CCRT). The SCC-Ag and CEA levels were measured before treatment, 1 month after treatment, and during the follow-up. The association between the pretreatment tumor marker levels and the clinical prognostic factors was evaluated. The frequency of complete remission (CR) and the normalization of the posttreatment tumor marker were also analyzed. The pretreatment serum levels of CEA and SCC-Ag were elevated in 68 (32.2%) and 148 (70.1%) patients, respectively. The number of patients with an elevated pretreatment SCC-Ag level was associated with the FIGO stage, tumor volume, and pelvic lymph node status. The pretreatment CEA was only significantly related to the tumor volume and pelvic lymph node involvement. One month after completing CCRT, the CEA and SCC-Ag levels were normalized in almost all patients with an incidence of 88.2% (60/68) and 93.2% (138/148), respectively. Among the patients who gained CR with a previously elevated pretreatment CEA and SCC-Ag, the values were normalized in 92.1% (58/63) and 96.4% (134/139) at 1 month, respectively. Combination assays of the pre- and posttreatment serum CEA and SCC-Ag levels appear to be useful for both predicting the prognosis and estimating the clinical response in cervical cancer. However, the routine combined measurement with SCC-Ag of CEA in all patients had limited additional effect in predicting the prognostic significance.     

Use of serum squamous cell carcinoma antigen assays in chemotherapy treatment of cervical cancer

Serum squamous cell carcinoma antigen levels of 15 patients with recurrent or progressive squamous cell carcinoma of the cervix on chemotherapy treatment were assayed. In 13 of these 15 patients (86.7%), clinical response was positive correlated with change in serum SCC level. A stationary or rising serum SCC level indicated that the disease is probably stationary or progressive and chemotherapy should be stopped or changed.     

Large cell neuroendocrine carcinoma of the cervix: prognostic factors and survival advantage with platinum chemotherapy

Objective

Large cell neuroendocrine carcinoma of the cervix (LCNEC) is a rare cervical neoplasm associated with poor survival. Our objective was to identify treatments associated with improved survival.

Methods

Relevant data were abstracted from an English literature MEDLINE search, SEER database, and a patient treated at our institution. Multivariate analysis was performed by generating Cox proportional hazard ratios.

Results

We identified 62 patients with LCNEC: 49 cases from the English literature, 12 patients in the SEER database and our patient. Out of the 62 women, median age was 37 (range, 21-75). FIGO stage was as follows: 58% had stage I disease, 16% had stage II, 2% had stage III, 8% had stage IV disease and 16% had no stage documented. Of all patients, 73% underwent primary surgery, 4.7% underwent primary radiation, 4.7% underwent chemotherapy, 8% had chemoradiation, and 9.6% had no primary treatment. Of all patients, 58% died of disease, 26% had no evidence of disease, 3% were alive with disease, and 13% had no survival data. The overall median survival was 16.5 months (0.5-151 months). Median overall survival for stage I, II, III, and IV cancers was 19, 17, 3, and 1.5 months, respectively. In a multivariate analysis, earlier stage (p < 0.00001) and the addition of chemotherapy (p = 0.04) were associated with improved survival. Both platinum agents (p = 0.034) and platinum and etoposide together (p = 0.027) were associated with improved survival.

Conclusions

Perioperative chemotherapy, in particular platinum with or without etoposide, improves survival in the rare LCNEC.     

Fever, haemoglobin and smoking as prognostic factors during the treatment of cervical carcinoma by radiotherapy

In a series of 151 patients diagnosed with cervical carcinoma the prognostic importance of temperature elevation, anaemia and smoking during radiotherapy was evaluated. Tumor necrosis and infection at the start of therapy were also analysed. A febrile reaction during irradiation seems to be an ominous sign with regard to tumour cure and survival rates. It was not possible to verify any enhancement of the radiotherapeutic effect by hyperthermia in the 38-40 degrees C body temperature range. A haemoglobin level less than 120 g/l and tumour necrosis were highly significantly associated with local treatment failure, tumour recurrences and decreased patient survival. Smoking during radiotherapy was a non-significant prognostic variable when tested by a multivariate technique.     

子宫颈鳞癌Ⅰb～Ⅱa期患者预后预测系统的建立及其临床意义

目的分析子宫颈鳞癌Ⅰb~Ⅱa期患者的预后影响因素并建立预后预测系统,以探讨其在指导术后辅助治疗中的作用。方法回顾性分析接受手术治疗的306例Ⅰb~Ⅱa期宫颈鳞癌患者的临床病理资料,对影响其预后的因素进行单因素和多因素分析。结果306例患者的5年生存率为78 1%。单因素分析结果显示,与其预后有关的因素为淋巴结转移、病理分化程度、肿瘤直径、宫旁组织浸润、深肌层浸润和脉管内瘤栓(P<0 05);多因素分析结果显示,淋巴结转移、深肌层浸润、宫旁组织浸润是影响其预后的独立危险因素(P<0 05)。根据危险因素的不同建立预后预测系统,即将患者分为低危组、中危组和高危组3组,其5年生存率分别为90 3%、83 9%和43 1%。低危组(无危险因素或仅宫旁组织浸润)局部复发的发生率仅为2 2%;中危组(深肌层浸润或合并有宫旁组织浸润)局部复发的发生率为13 5%,远处转移的发生率为1 3%, 局部复发合并远处转移的发生率为0 6%;高危组(淋巴结转移或合并其他危险因素)局部复发和远处转移的发生率分别为25 9%和48 3%,局部复发合并远处转移的发生率为10 3%。结论淋巴结转移、深肌层浸润、宫旁组织浸润是影响Ⅰb~Ⅱa期宫颈鳞癌患者预后的独立因素;根据预后影响因素建立的预后预测系统有助于指导术后辅助治疗。     

Immunohistochemical study of carcinoembryonic antigen of the tissue and cell levels in adenocarcinoma of the uterus

Immunohistochemical staining was performed for carcinoembryonic antigen (CEA) in tissues taken from 41 cases of cervical and 67 cases of endometrial adenocarcinomas. Utilizing this method, smear specimens from 21 cases with cervical and 25 cases with endometrial adenocarcinomas were investigated at the cell level. The results: 1) The investigation at the tissue level indicated that CEA staining was positive in 80% of cases of cervical adenocarcinoma. On the other hand, the positive rate was as low as 55% of the endometrial adenocarcinoma cases. It further declined to 35% when limited to pure adenocarcinoma without squamous elements. In addition, a difference was recognized between the cervical and endometrial groups in their localization. It was apparent that while even the cytoplasm in most of the cervical adenocarcinoma appeared to be markedly stained, such a tendency was observed and was weak in only a part of the cell membrane in the endometrial adenocarcinoma cases. 2) The studies with smear specimens indicated that while 57% (13/21) of the cervical adenocarcinoma cases were CEA positive, only 12% (3/25) were positive in endometrial adenocarcinoma cases. Therefore, a difference was recognized between the two at the cell level in their CEA staining characteristics. 3) Our observation revealed that CEA was more prominent in the poorly differentiated type than in the well differentiated one, in both cervical and endometrial adenocarcinoma. This seems to indicate a relationship between the histological differentiation and production of CEA. On the basis of the above findings, it was inferred that although both cervical and endometrial adenocarcinoma occur in the common Müllerian duct organ, they might have different biological characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)     

Squamous cell carcinoma antigen in patients with cancer of the uterine cervix

The serum concentrations of the tumor-associated antigen SCC were determined in 62 patients with invasive carcinoma of the uterine cervix. Antigen values above 2.0 ng/ml were considered as slightly positive, and those above 4.0 ng/ml as highly positive. Pretherapeutic levels were elevated (greater than 2.0 ng/ml) in 68% of the patients with cervical carcinoma. In 49 patients with carcinoma in situ, 18% of the SCC values were above the normal range. The greatest incidence of positive SCC titers (84%) was observed in women with recurrent cervical carcinoma. Only 6.7% of women in remission had elevated titers. Five of 24 cases (21%) with invasive endometrial carcinoma had SCC values exceeding 2.0 ng/ml. Slightly positive levels of tumor antigen were seen in 1.8% (1/56) of the control subjects. Serial SCC determinations revealed a correlation with the clinical course of disease in 84%. The determination of SCC is useful for the surveillance of patients with cervical squamous cell carcinoma.     

Characterization and localization of carcinoembryonic antigen in a suqauamous cell carcinoma of the cervix.

The carcinoembryonic antigen (CEA) of a patient with squamous cell carcinoma of the cervix whose plasma CEA titer was 28 μg/ml and tumor CEA concentration was 900 μg/g was subjected to immunological and physicochemical analyses. By means of immunodiffusion and immunoelectrophoresis, cervical cancer CEA was found to be immunologically identical to colonic cancer CEA. However, cervical cancer CEA appeared in gel filtration to be 370,000 in molecular size, thus being appreciably larger than the 200,000 size CEA usually found in colonic carcinomas. The CEA in this squamous cell carcinoma of the cervix was localized by an immunoperoxidase reaction performed on paraffin sections of the tumor and was found to be almost exclusively present on the surface of the tumor cells. It appears that this immunocytochemical procedure for CEA detection and localization can be employed in the routine histopathological evaluation of such neoplastic tissues.     

P63 and EGFR as prognostic predictors in stage IIB radiation-treated cervical squamous cell carcinoma

OBJECTIVES: The purpose of this study was to determine the relation between p63, p53-related gene, epidermal growth factor receptor (EGFR), and spontaneous apoptosis in relation to radiotherapy in patients with FIGO stage IIB cervical carcinoma, who had undergone radiation and concurrent chemotherapy, retrospectively. METHODS: Eighty-four patients with FIGO stage IIB squamous cell carcinoma (SCC) of the uterine cervix, who were treated with radiotherapy and concurrent chemotherapy between 1991 and 1996, were included in the present study. The clinicopathologic features, patterns of treatment failure, and survival data were compared with the expressions of p63 and EGFR, which were determined by immunohistochemistry and with apoptosis by TUNEL on tissue-arrayed slides. Univariate and multivariate analyses were performed to determine the prognostic factors that influence patient survival. RESULTS: Overall the indices of the expressions of p63 and EGFR in stage IIB cervical carcinoma were 18.7 and 26.6%, respectively, and these were found to be correlated. EGFR expression was significantly associated with extrapelvic failure (P = 0.03), whereas p63 was associated with locoregional failure (P = 0.03). The spontaneous apoptotic index showed no prognostic value, but the immunoreactivities of p63 and EGFR were associated with a worse prognosis by both univariate (P = 0.01 and 0.04, respectively) and multivariate analysis (95% CI:2.0-4.4, RR:3.2 and 95% CI:4.9-8.7, RR:6.7, respectively). CONCLUSIONS: The expression of p63 gene is associated with poor survival and locoregional failure, whereas EGFR expression was found to be a prognostic predictor of extrapelvic failure. Both molecules were found to be potent molecular risk factors in patients with FIGO stage IIB SCC of the uterine cervix, who had received radiotherapy and concurrent chemotherapy.     

Squamous cell carcinoma of the bladder presenting as vulvitis and cliteromegaly

INTRODUCTION: Clitoral metastases are exceptionally rare. We present a case of a squamous cell carcinoma of the bladder presenting with a clitoral metastasis. CASE REPORT: We report the case of an 84-year-old lady with frequency, dysuria and a clitoral mass, which was found to be a poorly differentiated carcinoma on fine needle aspiration cytology. Cystoscopy revealed a moderate to poorly differentiated squamous cell carcinoma of the bladder. CONCLUSION: This is the first reported case of a squamous cell carcinoma of the bladder with clitoral metastasis. Clitoral metastases are exceptionally rare, with only seven previous cases reported in the literature. Although the commonest cause of cliteromegaly is hormonal, a metastatic carcinoma should be considered as part of the differential diagnosis in the elderly female.     

Power Doppler vascularity index for predicting the response of neoadjuvant chemotherapy in cervical carcinoma

BACKGROUND: To evaluate whether the power Doppler vascularity index (PDVI) can predict the response to neoadjuvant chemotherapy (NACT) in cervical carcinoma. METHODS: Twenty-five women with bulky early stage cervical carcinoma treated by NACT followed by surgery were enrolled. Their response to NACT was evaluated. Clinical characteristics and pathologic data were recorded. Transvaginal power Doppler was performed before, during and after NACT. PDVI was detected using power Doppler and a quantitative image processing system. Factors that can potentially correlate with the response to NACT were analyzed. RESULTS: Twelve (48%) patients showed a response (responders) to NACT and 13 (52%) were unchanged or had progressive disease (nonresponders) after NACT. Higher PDVI values were noted in tumors with lymphovascular emboli and pelvic lymph node metastasis both before and after NACT. The mean values of the PDVI of the nonresponders before (19.27 +/- 6.01 vs. 12.28 +/- 7.06, p = 0.014), during (20.2 +/- 1.5 vs. 12.9 +/- 2.1, p = 0.009) and after NACT (18.1 +/- 6.0 vs. 9.3 +/- 5.4, p = 0.001) were significantly higher than those of the responders. When the cutoff point for predicting nonresponders to NACT was set at a PDVI value of 15%, the sensitivity was 92.3% and the specificity 66.7%. CONCLUSIONS: The power Doppler vascularity index can predict the response to neoadjuvant chemotherapy in cervical cancer, and might be useful for the evaluation of response to chemotherapy in cancer patients in the future.     

CD44 isoform 6 (CD44v6) is a prognostic indicator of the response to neoadjuvant chemotherapy in cervical carcinoma

OBJECTIVE: Theclinical efficacy of neoadjuvant chemotherapy (NAC) in distinct groups of cervical cancer patients has been well documented, but parameters at the cellular level regulating the different responsiveness to this treatment have not been adequately explored. METHOD: A series of 21 patients with stage Ib and IIa bulky cervical carcinomas were treated by preoperative NAC with three courses of cisplatin, epirubicin, etoposide, and bleomycin prior to radical hysterectomy, and subsequently followed up for a mean of 52.3 months. Biopsies taken prior to NAC and operative specimens were subjected to immunohistochemical (IHC) staining for alpha-catenin, beta-catenin, E-cadherin, and CD44 isoform 6 (CD44v6), to uncover the role of adhesion molecules as determinants of the response to NAC and disease outcome. RESULTS: Seven of the twenty-one (33.3%) women died of the disease; adenosquamous (n = 4 cases) histology (RR 4.50, 95% CI 1.85-10.68) and lymph node involvement (RR 6.00, 95% CI 0.42-85.26) were significant determinants of nonsurvival. All 21 carcinomas were human papillomavirus DNA positive. The factors predicting the response to NAC in univariate analysis were: CD44v6 expression in the pre-NAC and post-NAC samples (P = 0.00056 and P = 0.00336, respectively). In multiple logistic regression analysis, the factors with independent predictive value for response to NAC were CD44v6 expression prior to (P = 0.0099) and after (P = 0.0470) NAC. In univariate survival analysis, the most significant (P < 0. 001) predictors of recurrence-free survival (RFS) were age and number of lymph nodes removed. In multivariate survival analysis, the independent predictor for RFS was only histological type (P = 0. 0064). Overall survival (OS) was predicted in a Cox model by recurrence (P = 0.0033), CD44v6 expression after NAC (P = 0.013), and patient's age (P = 0.039). CONCLUSIONS: These data indicate that CD44v6 is involved in the response to NAC, and eventually in disease outcome. This implicates that the assessment of CD44v6 expression might help in selecting patients who are likely to respond to NAC, i. e., women with significantly reduced CD44v6 expression in their tumors before treatment. Noteworthy, the response to NAC did not predict a favorable disease outcome.