Post-treatment serial serum squamous cell carcinoma antigen (SCC) in the monitoring of squamous cell carcinoma of the cervix

Serum squamous cell carcinoma antigen (SCC) was raised in 62% of 308 patients with squamous cell carcinoma of the cervix before treatment. Post-treatment SCC levels were raised in 69 patients (22.4%). Retrospective review showed that persistently raised SCC level after treatment was significantly associated with persistent or recurrent disease in squamous cell carcinoma of the cervix. The specificity of persistently raised SCC level in association with recurrent disease was 98.2%. The sensitivity in association with recurrent disease was 74.7%. The positive predictive values was 94.2%. The median lead time for recurrence was 4 months. SCC was raised in 38% of patients with clinical evidence of disease in the vagina. One patient had raised SCC one month prior to clinical detection of vaginal metastasis and was salvaged by an exenterative procedure. SCC was raised in 71–91% of patients with metastatic disease in the lung, lymph nodes or other distant sites. Thus, persistently raised SCC level after treatment of squamous cell carcinoma should alert the clinician to look for recurrent disease especially in distant metastatic sites. Post-treatment raised SCC level was associated with less than 5% 5-year survival rate whereas in patients with normal SCC level, the 5-year survival rate was 87%.     

Pulmonary tumor embolism from squamous cell carcinoma of the vulva

Involvement of the pulmonary vessels by tumor emboli has been described from different primary sites of malignancy. A case of pulmonary tumor embolism due to squamous cell carcinoma of the vulva is reported. This form of pulmonary involvement has not previously been described in cases of vulvar carcinoma and it is rare in gynecologic neoplasms. The development of dyspnea with rapid clinical deterioration and fatality associated with multiple pulmonary emboli and histologic signs of pulmonary hypertension is well shown by this case.     

An evaluation of squamous cell carcinoma antigen in patients with cervical squamous cell carcinoma

In a prospective study, serum concentrations of squamous cell carcinoma antigen, a subfraction of tumor antigen (TA-4), were determined by radioimmunoassay from healthy donors, pregnant women, and subjects with various benign and malignant gynecologic diseases. Ninety-six percent of 99 healthy persons including all 52 female controls, the 15 pregnant patients, and all 23 subjects with benign gynecologic tumors, had squamous cell carcinoma antigen levels less than 2.0 ng/ml. Seven of 51 (14%) patients with cervical intraepithelial neoplasia and 16 of 24 (67%) patients with cervical squamous cell carcinoma had squamous cell carcinoma antigen levels greater than 2.0 ng/ml. Declining and rising levels of squamous cell carcinoma antigen, which were determined sequentially in nine cases of cervical carcinoma that were associated with elevated pretreatment levels of squamous cell carcinoma antigen, correlated with regression and progression of the disease. Serial serum levels of squamous cell carcinoma antigen provide a noninvasive means of monitoring the effects of individual therapy in patients with cervical squamous cell carcinoma.     

Significance of lymphoplasmocytic infiltration around tumor cell in the prediction of regional lymph node metastases in patients with invasive squamous cell carcinoma of the vulva: a clinicopathologic study

Histologic material from 42 patients treated for invasive squamous cell carcinoma of the vulva was studied to determine the prognostic significance of lymphoplasmocytic infiltration around tumor cells in the prediction of regional lymph node metastases. No correlation was found between lymphoplasmocytic infiltration and nodal metastasis with respect to degree of tumor differentiation, stage of disease, and vascular channel involvement. The presence or absence of lymphoplasmocytic infiltration around tumor cells appears to have no prognostic value in predicting nodal metastases.     

Microinvasive squamous cell carcinoma of the vulva

Six patients with microinvasive squamous cell carcinoma of the vulva were evaluated. None of the patients had carcinoma that invaded the stroma to the depth of more than 3 mm. One had positive lymph nodes and died as a result of nodal involvement. The management of patients with vulvar carcinoma is discussed.     

子宫颈鳞状细胞癌复发患者血清鳞状细胞癌抗原监测的意义

目的探讨血清鳞状细胞癌抗原（SCCAg）在监测宫颈鳞癌患者复发中的意义。方法对1999-2005年收治的72例宫颈鳞癌复发患者血清SCCAg水平与诊断、预后的关系进行单因素和多因素分析。结果72例复发患者中,术后复发30例、放化疗后复发42例,其中血清SCCAg水平升高者61例（占85％）。此61例患者中,20例在随诊中首先出现血清SCCAg水平升高而临床及影像学检查未发现肿瘤,血清SCCAg水平提前升高的中位时间为3个月,平均4．6个月（1～13个月）。72例复发患者中,45例患者无任何临床症状,仅因血清SCCAg水平升高或常规随诊发现复发;27例患者有症状,其中单侧下肢水肿或疼痛15例,阴道不规则流血7例,出现远处转移相关症状5例。细胞或组织病理学检查诊断复发者33例;临床及影像学检查结合血清SCCAg水平诊断复发者39例,其中29例仅依靠血清SCCAg水平升高及影像学检查即诊断复发。72例复发患者的中位生存时间为11个月,平均生存时间为23个月（2～62个月）,总的3年生存率为25％,5年生存率为19％。单因素分析发现,初治前患者血清SCCAg水平、病理分级、复发部位、复发后治疗方式以及复发时、复发后治疗中、治疗后血清SCCAg水平对患者的3年生存率有明显影响（P〈0．01）;但20例血清SCCAg水平提前出现升高的患者与52例血清SCCAg水平未提前升高的患者相比,3年生存率分别为22％、27％,差异无统计学意义（P=0．5761）。多因素分析发现,复发患者仅病理分级、复发后的治疗方式是独立的预后影响因素（P〈0．05）;而复发部位及各种血清SCCAg状态不是独立的预后影响因素（P〉0．05）。结论血清SCCAg水平监测在宫颈鳞癌复发患者中的诊断及其对预后的判断中有一定的价值。     

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.     

Pretreatment levels of serum squamous cell carcinoma antigen and urine polyamines in women with squamous cell carcinoma of the cervix.

OBJECTIVES: To investigate whether pretreatment levels of serum squamous cell carcinoma antigen (SCCA) and urine polyamines can predict lymph node metastases in patients with early stage cervical carcinoma. METHODS: Pretreatment measurement of serum SCCA and urine polyamine levels was carried out for 419 women. Of those women, 104 with stage IB and IIA cancer received radical surgery and had tumor size reassessed postoperatively. RESULTS: The women had increased levels of serum SCCA (>2.0 ng/mL) and elevated urine polyamines (>45 micromol/g of creatinine) with advanced cancer stage (P<0.01). The median SCCA level was significantly higher in women with metastatic disease than that in those without lymph node involvement (3.9 vs. 1.1; P<0.01). Women with nodal involvement also had significantly higher median levels of urine polyamines than those without nodal disease. CONCLUSIONS: Pretreatment measurement of SCCA and urine polyamine levels may help in predicting lymph node metastases in women with early stage cervical carcinoma.     

Long-term survival and disease recurrence in patients with primary squamous cell carcinoma of the vulva

OBJECTIVES: To assess time to failure and sites of failure with extended follow-up of patients with squamous cell carcinoma (SCC) of the vulva. METHODS: A retrospective analysis of 330 patients with primary SCC of the vulva treated at Mayo Clinic between 1955 and 1990 was conducted. The main outcome measures were the rates of treatment failure. The Kaplan-Meier method and the log-rank test were used to estimate the rates of overall survival, disease-free survival, and recurrence. The Cox proportional hazards model was used to assess independent variables as prognostic factors for treatment failure. RESULTS: All 330 patients in the cohort underwent lymphadenectomy; 113 patients (34.2%) had involvement of the inguinofemoral nodes and 88 patients (26.7%) had treatment failure. Treatment failures occurred more frequently in patients who presented with inguinal metastasis at the primary surgery and during the first 2 years of follow-up. After 2 years, both groups, with or without positive inguinal nodes, had similar treatment failure rates. Most patients with disease recurrence in the groin died within the first 2 years of follow-up. Involvement of the inguinal nodes was the main independent predictive factor for survival, disease recurrence, and metastasis. CONCLUSIONS: Most treatment failures occurred during the 2 years after initial surgical management. However, in 35% of patients, disease reoccurred 5 years or more after diagnosis, which demonstrates the need for long-term follow-up. Complete ipsilateral or bilateral inguinofemoral lymph node dissection ensures a thorough evaluation and treatment of the groin.     

Does preoperative serum squamous cell carcinoma antigen level predict occult extracervical disease in patients with stage Ib invasive squamous cell carcinoma of the cervix?

Preoperative serum squamous cell carcinoma antigen levels were obtained from 65 patients with International Federation of Gynecology and Obstetrics stage Ib invasive squamous cervical cancer before planned radical hysterectomy to determine whether elevated squamous cell carcinoma antigen levels (greater than 2.5 ng/mL) predicted occult extracervical extension of disease. Although the specificity of a normal level was good (0.91), the sensitivity of an elevated level was only 0.68. Not all patients with nodal metastases had elevated serum squamous cell carcinoma antigen levels; in particular, no patient with occult para-aortic nodal disease had elevated serum squamous cell carcinoma antigen.     

Invasive squamous carcinoma of the vulva in young patients

Over a 30-year period, 17 patients below the age of 35 with invasive squamous carcinoma of the vulva were identified, 8 of whom (47.1%) had “microinvasive” disease. Venereal diseases and condyloma accuminata were not predisposing factors. Immunosuppression was a contributory factor in 2 patients. Although carcinoma in situ was antecedent in only 1 patient, it was an associated lesion in 87.5% of patients with “microinvasive” and 22.2% of patients with invasive carcinoma. The nature and course of this disease in young patients do not differ from the elder counterpart. Prolonged follow-up of these patients has revealed increased susceptibility of the perineum, vagina, and cervix to multiple neoplasms.     

鳞状细胞癌抗原与子宫颈鳞状细胞癌的临床病理特征及预后的关系

目的 探讨治疗前血清鳞状细胞癌抗原（SCCAg）滴度与宫颈鳞状细胞癌（鳞癌）临床病理特征的关系,以及作为预测预后的因素的意义。方法 选择114例治疗前检测过血清SCCAg并经治疗后长期随访的Ⅰb1～Ⅱa期宫颈鳞癌患者,结合临床资料对SCCAg与临床病理特征及预后的关系进行单因素和多因素分析。结果 单因素分析显示,治疗前血清SCCAg滴度升高（正常值≤1．5mg／L）与肿瘤直径、深肌层浸润及盆腔淋巴结转移相关（P〈0．05）;多因素分析显示,SCCAg滴度升高与深肌层浸润（P=0．029）、盆腔淋巴结转移（P=0．049）相关。114例患者的5年累积无瘤生存率为78．6％,总复发率为27．2％。单因素分析显示,SCCAg滴度升高、盆腔淋巴结转移与5年累积无瘤生存率及复发相关（P〈0．05）;多因素分析显示,影响预后的独立因素为SCCAg滴度升高（P=0．030）和盆腔淋巴结转移（P=0．003）,影响复发的显著相关因素为盆腔淋巴结转移（P=0．006）。盆腔淋巴结转移且SCCAg滴度正常者与盆腔淋巴结转移且SCCAg滴度升高者,5年累积无瘤生存率（分别为50．0％、50．9％）、复发率[分别为60．0％（6／10）、47．1％（8／17）]、局部复发率[分别为3／8、20．0％（3／15）]和远处复发率[分别为1／8、20．0％（3／15）]分别比较,差异均无统计学意义（P〉0．05）。盆腔淋巴结无转移且SCCAg滴度正常者与盆腔淋巴结无转移且SCCAg滴度升高者,5年累积无瘤生存率（分别为98．0％、71．8％,P=0．003）、复发率[分别为9．8％（5／51）、33．3％（12／36）,P=0．006]、局部复发率[分别为2．1％（1／47）、26．5％（9／34）,P=0．001]分别比较,差异均有统计学意义。结论 治疗前血清SCCAg滴度升高和盆腔淋巴结转移是影响Ⅰb1～Ⅱa期宫颈鳞癌患者预后的独立因素。治疗前血清SCCAg滴度升高且盆腔淋巴结无转移患者的局部复发风险显著升高。     

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.     

Regulation of apoptosis in squamous cell carcinoma of the vulva

OBJECTIVE: To analyze the expression of Bcl-2, Bax and ICH-1-L in squamous cell cancer of the vulva. STUDY DESIGN: Slides of 72 vulvar squamous cell carcinomas were stained immunohistologically for Bcl-2, Bax and ICH-1-L. They were analyzed for the percentage of positive tumor cells, staining intensity and pattern, and amount of Bcl-2-positive lymphocytes around the tumor. Results were analyzed for correlations with clinical and histologic characteristics. Disease-free and overall survival were evaluated by Kaplan-Meier curves with the log-rank test. RESULTS: Strong expression of Bcl-2 was present in 15% of tumors. Carcinomas with high Bcl-2 expression more frequently had lymph node metastasis (P = .03), without significant differences in other clinical or histologic parameters, disease-free and overall survival. Strong Bax expression was observed in 57%, without prognostic significance. Carcinomas showed high ICH-1-L expression in 35%. These tumors seemed to have longer disease-free survival, while overall survival was significantly longer (P = .02). A strong Bcl-2-positive inflammatory infiltrate was highly predictive of lymph node metastasis (P = .02) and disease-free survival (P = .03). CONCLUSION: In squamous cell carcinoma of the vulva, inhibition of apoptosis is associated with a more-aggressive phenotype, and a Bcl-2-positive inflammatory infiltrate is predictive of prognosis. A study with more patients should confirm the importance of apoptosis in vulvar carcinoma.     

Tumor proliferation in squamous cell carcinoma of the vulva.

Tumor proliferation is of important prognostic significance for several neoplasms. The very few previous studies on this parameter in vulvar carcinoma have shown contradictory results. The aim of this study was to determine the prognostic significance of tumor proliferation in vulvar carcinoma. Paraffin-embedded tissue of 74 squamous cell carcinomas of the vulva was immunostained for MIB-1, detecting Ki-67, and analyzed for staining patterns and the percentage of positive cells. There were three general staining patterns: a diffuse distribution (diffuse type), a localized staining at the infiltrating tumor border (infiltrating type), and a localized staining in basal parts of infiltrating tumor cell aggregates (basal type). The percentage of positive cells was not correlated with morphologic or clinical parameters, nor was it correlated with disease-free and overall survival. MIB-1 staining types were correlated with tumor type and grading. Tumors of diffuse and infiltrating type seemed to have more frequent lymph node metastasis (p = 0.053) and shorter disease-free survival (p = 0.076). In these tumors, overall survival time was reduced significantly (p = 0.02). In multivariate analysis, MIB-1 staining types were the most important factor for overall survival with an odds ratio of 4.73. In conclusion, distribution and not the percentage of proliferating cells is of prognostic significance in squamous cell carcinoma of the vulva.     

Radical vulvectomy for squamous cell carcinoma of the vulva

Twenty-one patients with squamous cell carcinoma of the vulva who were subjected to radical vulvectomy and inguinal-pelvic lymphadenectomy were studied. The overall mortality rate was 24%. Operative- and tumor-related mortalities were 9.5% and 14.2%, respectively. Recurrence was seen in 5 patients. The most common complication was wound infection and breakdown.