Clinical significance of squamous cell carcinoma antigen in cancer of the human uterine cervix. Comparison with CEA and CA-125.

Serum squamous cell carcinoma antigen (SCCa) concentrations were determined by a radioimmunoassay kit before and during the treatment of 50 patients with cervical carcinoma: 44 with squamous cell carcinoma (SCC) and 6 with adenocarcinoma. The positivity rate of SCCa was 50% (52% for SCC and 33% for adenocarcinoma). The sensitivity of SCCa for SCC was twice as high as that of CEA and CA-125. Low serum concentrations were observed in early-stage carcinoma, indicating that SCCa is not useful for diagnosis. In advanced cases, serum levels were directly and significantly correlated with the stage of the disease.     

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。     

Tumor markers CA 125, squamous cell carcinoma antigen, and carcinoembryonic antigen in patients with adenocarcinoma of the uterine cervix

Between 1978-1987, 439 patients with primary cervical carcinoma were admitted to our department. Seventy-seven patients (17.5%) had cervical adenocarcinoma and are reviewed in this retrospective study. Serial serum samples of these 77 patients were analyzed for cancer antigen 125 (CA 125), squamous cell carcinoma antigen, and carcinoembryonic antigen. Before treatment, only elevated serum CA 125 levels varied directly with the clinical stage of disease. In stages IB and II disease (International Federation of Gynecology and Obstetrics [FIGO]), the incidence of elevated serum CA 125 levels was highest in patients with adenosquamous tumor. Serum marker levels, measured 3 months after therapy, concurred with the treatment results. At that time, 17 of the 23 cases (74%) with at least one elevated serum marker level either had residual disease (N = 9) or developed recurrent disease during follow-up (N = 8), compared with six of the 40 cases (15%) with normal serum marker levels (P less than .001). Increasing serum marker levels during follow-up coincided with or preceded the clinical detection of recurrent disease. Tumor relapse, clinically located in the vaginal vault, occurred concomitant with a rise of at least one serum marker level in six of the seven cases (86%). All 15 patients with abdominal recurrence showed elevation of CA 125. In progressive disease, very high serum CA 125, squamous cell carcinoma antigen, and carcinoembryonic antigen levels were determined in patients with adenosquamous tumor, whereas patients with adenocarcinoma demonstrated only high CA 125 levels. We conclude that all three markers are important for monitoring patients with cervical adenocarcinoma.     

Determination of squamous cell carcinoma antigen in the blood of patients with cancer of the uterine cervix

The RIA method has been used to assay the squamous cell carcinoma antigen in the serum of twenty-four patients suffering from cervical cancer. The results obtained showed expressive differences between the levels in women with metastatic relapse and in those in remission, but the SCC antigen is particularly useful in the therapeutic monitoring, since it can assess of the current treatment.     

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.     

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.     

Hypercalcemia in patients with squamous cell carcinoma of the cervix.

Hypercalcemia was identified in approximately 1% of the patients with epidermoid cervical cancer admitted to the gynecologic oncology service at LAC/USC Women's Hospital over a 6.5-year period. Nonspecific neurologic manifestations of weakness, obtundation, and coma were the predominant presenting features. The response to anticalcemic therapy depended upon the extent of the underlying malignancy and the presence of uremia. The appearance of hypercalcemia in these patients usually signified a rapidly deteriorating clinical course which was irreversible despite aggressive medical management in some instances. Recent concepts in the humoral mechanisms of cancer related hypercalcemia, briefly reviewed here, may provide safer and more successful avenues of treatment for salvageable patients in the near future.     

Peritoneal cytology in patients with squamous cell carcinoma of the cervix

The importance of peritoneal cytology was investigated in 163 patients with squamous cell carcinoma of the cervix. Of 116 patients undergoing primary evaluation and treatment 3 (2.5%) had abnormal cytology. No abnormal specimens were found in 77 patients undergoing radical hysterectomy. Five (10.6%) of forty-seven patients evaluated and treated for post-treatment recurrence had abnormal cytology. All eight patients with abnormal cytology had other poor prognostic factors and are dead of cancer. The relevance of abnormal cytology is discussed.     

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。     

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.     

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%.     

Comparison of biological behavior between early-stage adenocarcinoma and squamous cell carcinoma of the uterine cervix

Objectives

(1) To compare the anatomopathological variables and recurrence rates in patients with early-stage adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the uterine cervix; (2) to identify the independent risk factors for recurrence.

Study design

This historical cohort study assessed 238 patients with carcinoma of the uterine cervix (IB and IIA), who underwent radical hysterectomy with pelvic lymph node dissection between 1980 and 1999. Comparison of category variables between the two histological types was carried out using the Pearson's χ²-test or Fisher exact test. Disease-free survival rates for AC and SCC were calculated using the Kaplan–Meier method and the curves were compared using the log-rank test. The Cox proportional hazards model was used to identify the independent risk factors for recurrence.

Results

There were 35 cases of AC (14.7%) and 203 of SCC (85.3%). AC presented lower histological grade than did SCC (grade 1: 68.6% versus 9.4%; p < 0.001), lower rate of lymphovascular space involvement (25.7% versus 53.7%; p = 0.002), lower rate of invasion into the middle or deep thirds of the uterine cervix (40.0% versus 80.8%; p < 0.001) and lower rate of lymph node metastasis (2.9% versus 16.3%; p = 0.036). Although the recurrence rate was lower for AC than for SCC (11.4% versus 15.8%), this difference was not statistically significant (p = 0.509). Multivariate analysis identified three independent risk factors for recurrence: presence of metastases in the pelvic lymph nodes, invasion of the deep third of the uterine cervix and absence of or slight inflammatory reaction in the cervix. When these variables were adjusted for the histological type and radiotherapy status, they remained in the model as independent risk factors.

Conclusion

The AC group showed less aggressive histological behavior than did the SCC group, but no difference in the disease-free survival rates was noted.     

血清SCCAg及CA125在诊断宫颈鳞癌及评价预后中作用的研究

目的:探讨血清SCCAg及CA125用于宫颈鳞癌诊断、手术治疗及预后的价值。方法:选取ⅠA2～ⅡA期宫颈鳞状细胞癌为研究组,20例CIN及20例慢性宫颈炎分别为对照组1和对照组2。采用固相夹心法酶联免疫吸附实验(ELISA)检测血清SCCAg的数值,采用化学发光免疫分析法(CLIA)检测血清CA125数值。比较分析血清SCCAg及CA125与宫颈鳞癌临床病理特征、手术疗效及预后的关系。结果:宫颈鳞癌组术前血清SCCAg及CA125水平均高于慢性宫颈炎组,差异均具有统计学意义(P<0.01)。宫颈鳞癌组术前SCCAg水平高于CIN组,差异有统计学意义(P<0.001);宫颈鳞癌组术前CA125水平与CIN组的差异无统计学意义(P=0.049,P>0.0167)。血清SCCAg、CA125诊断宫颈鳞癌的临界值分别为1.03ng/ml、8.16U/ml。血清SCCAg、CA125及两项联合诊断宫颈癌的ROC曲线下面积分别为0.954、0.718、0.960,两项联合后诊断性能无明显增加。宫颈鳞癌术前血清SCCAg随临床分期增加具有线性增加的趋势。脉管有否癌栓、盆腔淋巴结有否转移也与术前血清SCCA水平有关,差异有统计学意义(P=0.011,P=0.043)。宫颈鳞癌组手术治疗后的血清SCCAg及CA125水平均有逐渐降低趋势,差异有统计学意义(P均<0.001)。结论:血清SCCAg对宫颈鳞癌有较高的诊断价值,可考虑作为诊断及手术疗效评估指标之一,有助于初步判断脉管及盆腔淋巴结转移。血清CA125对于宫颈鳞癌诊断、手术评估及随访的价值均低于SCCAg,与SCCAg联合不能增加诊断的敏感度和特异度。     

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.     

Is CA-125 monitoring useful in patients with epithelial ovarian carcinoma and preoperative negative CA-125 serum levels?

Between December 1983 and December 1988 we examined the postoperative tumor marker development and correlated this to the clinical course of the disease in 56 patients suffering from primary epithelial ovarian carcinoma of International Federation of Gynecology and Obstetrics stages I-III and with a preoperative CA-125 serum level less than or equal to 65 U/ml. In 54% of all cases there was a reduction of more than 50% of the CA-125 serum level within the first 3 months after surgery. Nine out of thirteen patients with progressive disease (69%) showed an increasing CA-125 serum level with a median lead time of 6 months (0-11 months) prior to clinical diagnosis. These preliminary results indicate that the monitoring of cancer patients with CA-125 tumor marker seems to be a useful method of early diagnosis of progressive disease even in patients with preoperative serum levels lower than 65 U/ml.     

T and B lymphocytes in patients with squamous cell carcinoma of the uterine cervix

Subpopulations of peripheral lymphocytes were enumerated in Japanese with squamous cell carcinoma of the uterine cervix. T lymphocyte counts were carried out in SRBC rosette tests and B lymphocyte counts by immunobead rosette tests using antibody-coated polyacrylamide beads. “Active”T lymphocytes were significantly depressed in patients with dysplasia, carcinoma in situ, and advanced carcinoma; number of “total” T lymphocytes was also significantly lower in those with carcinoma in situ as compared to healthy controls. There was a decreased number of “total” B lymphocytes in patients with advanced carcinoma, and an increased number of IgA-bearing B lymphocytes in stage II invasive carcinoma, respectively. The present findings suggest that depression of cell-mediated immunity associated with T lymphocytes is responsible for the initiation of cervical carcinoma.     

Serum squamous cell carcinoma antigen in the monitoring of radiotherapy treatment response in carcinoma of the cervix

In this study, squamous cell carcinoma antigen (SCC) was detected in 96 of 157 patients with squamous cell carcinoma of the cervix and the percentage of patients with raised SCC levels increased with the stage of disease (P less than 0.01). The use of serial SCC assays and cervical biopsy histology during the course of radiotherapy to predict tumor response to irradiation was assessed. In patients who were given external irradiation before intracavitary radium, a high SCC level or the presence of viable tumor cells in the biopsy was found to be of no predictive value. However, at completion of radiotherapy, i.e., after intracavitary radium application, patients with persistently high SCC levels had a significantly higher incidence of residual tumor than patients whose SCC levels returned to normal (P less than 0.01). In 60% of patients with a persistently high SCC level, viable tumor was found in the cervical biopsy at the end of radiotherapy. On the other hand, only 5.4% of patients whose SCC level returned to normal had residual tumor.     

The role of pretreatment squamous cell carcinoma antigen level in locally advanced squamous cell carcinoma of the uterine cervix treated by radiotherapy

The purpose of this study was to determine the pretreatment serum squamous cell carcinoma antigen (SCC-ag) level as a generally applicable measurement in predicting and estimating the treatment outcome of patients with locally advanced SCC of the cervix. Three hundred fifty-two patients with stage IIB-IVA SCC of the cervix were managed with both external irradiation and high-dose rate intracavitary brachytherapy. A significantly higher median SCC-ag was seen in association with increasing stage, tumor size, and lymph node involvement. The difference in disease-free survival (DFS) between stages IIB and III patients was not statistically significant with SCC-ag level <2 ng/mL. In multivariate analysis, median SCC-ag level (> or =6.0 ng/mL) and lymph node metastases had significant independent effects on absolute survival and DFS. A direct linear relationship (y=-2.932x+ 84.896) existed between the median SCC-ag of groups distributed by pretreatment prognostic factors and the 5-year DFS rate. The 5-year DFS rate as a function of SCC-ag level defined by cervix size, lymph node status, and hydronephrosis was obtained from a formula combining risk scores and the baseline survival function. From the obtained formulas, we can objectively estimate the treatment outcome in patients with locally advanced squamous cell cervical cancer.