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.     

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。     

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.     

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.     

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.     

Peritoneal cytology in patients with carcinoma of the uterine cervix

Peritoneal cytology was obtained in 125 patients with carcinoma of the uterine cervix at the time of laparotomy. The incidence of positive peritoneal cytology was 11.2%. Positive peritoneal cytology was found four times more frequently in adenocarcinoma than in squamous cell carcinoma. The incidence of pelvic lymph node and paraaortic lymph node metastasis was higher in patients with positive peritoneal cytology than in patients with negative peritoneal cytology. The 2-year survival rate in patients with positive peritoneal cytology was 30.0% and it was 82.7% in patients with negative peritoneal cytology. Some patients (28.6%) with positive peritoneal cytology developed peritonitis carcinomatosa. It was concluded that it is very important to obtain peritoneal cytology routinely at the time of laparotomy in patients with carcinoma of the cervix.     

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 of the uterine cervix in association with stage 0 chronic lymphocytic leukemia/small lymphocytic lymphoma

BACKGROUND: There have been many cases of multiple malignant neoplasms involving the female genital tract reported, but involvement by epithelial and hematologic malignancy is extremely rare. CASE: A 52-year-old woman, who was followed for stage 0 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), had developed invasive squamous cell carcinoma of the uterine cervix. Microscopic examination of the hysterectomy specimen disclosed invasive squamous cell carcinoma in the cervix and monotonous populations of small lymphoid cells with proliferation centers, which are consistent with CLL/SLL, in the cervix as well as parametrium. Thirty months after the initial diagnosis of CLL/SLL, the patient died with systemic dissemination of squamous cell carcinoma, but the CLL/SLL remained a local disease. CONCLUSION: The clinical course of squamous cell carcinoma in this case appeared to be aggressive, but it was unclear whether the outcome was associated with an altered immune status due to the presence of concurrent CLL/SLL.     

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。     

Clinical analysis of patients operated with squamous cell carcinoma of the uterine cervix]

OBJECTIVES: The aim of our study was clinical analysis of patients operated with squamous cell carcinoma of the uterine cervix. MATERIALS AND METHODS: Between 1972 and 1991 at the 2nd Department of Obstetrics and Gynecology Medical University of Gdańsk 687 total hysterectomies in Wertheim-Meigs method were performed in the patients with, various clinical stages cervical carcinoma. The clinical analysis has been done in 499 patients with diagnosed invasive cervical cancer stages Ia2, Ib and IIa. The clinical progression of cancer was established on the basis of FIGO classification from the year 1985. In the 18 patients invasive cervical cancer occurred together with a pregnancy (cervical cancer was diagnosed in the I, II and III trimester). In this group squamous carcinoma was diagnosed in 16 cases (88.8%). Endocervical type was diagnosed in 8 cases (1.6%), among which 4 cases were of a squamous type (0.8%). Two 10-year-periods of time have been separated: since 01.01.1972 to 31.12.1981 and since 01.01.1982 to 31.12.1991. RESULTS AND CONCLUSIONS: In the studied 20-year period (1972-1991) in all 499 performed operations squamous carcinoma was the most often occurring histological type of cervical cancer--439 cases (88.0). Comparing the incidence of squamous carcinoma in both 10-year periods of time there were no significant differences (only almost a 3-fold decrease of the incidence of microcellular cancer in the second decade was observed). It was stated that a percentage share of squamous carcinoma in the clinical stages Ib and IIa did not change. The number of pregnancies and labours in the patients with squamous carcinoma was close to the patients with other histological types of cervical cancer. The mean age of patients with squamous carcinoma was 45.6 (22-74) and was lower than the age of patients with adenocarcinoma--49.1 years (22-73). The clinical symptoms of a cancer occurred in 81.4% of the studied group. Asymptomatic course was seen in 18.6% of patients. The incidence of positive lymph nodes in the patients with squamous carcinoma stages Ib-IIa was close to the patients with carcinoma adenosquamous (25.0% and 23.7% respectively) and lower than in the case of adenocarcinoma (34%) or anaplastic carcinoma (33.3%, because of a small number of patients in this group the figures are not reliable). In the patients with squamous carcinoma the highest 5-year survival (almost 80.4%) was stated.     

Squamous cell carcinoma in situ from the uterine cervix to the distal end of the fallopian tube.

An unusual case of squamous cell carcinoma of the uterine cervix is described in which spread occurred intraepithelially along the endometrium and one of the fallopian tubes. This marked superficial extension is an example of abnormal spread of a malignant tumour whose prognostic significance is unknown.     

A survey of tumor markers in patients with squamous cell carcinoma of the uterine cervix

The circulating levels of carcinoembryonic antigen (CEA), α-fetoprotein (AFP), and chorionic gonadotrophin (B-hCG) were correlated with the extent of disease in 47 patients with squamous cell carcinoma of the uterine cervix. Pretherapy serum CEA levels were elevated (> 10 ng/ml) in 12 of 47 (26%) of the patients. The greatest incidence and the highest CEA elevations were observed in the sera of patients with Stage III disease. No elevations of serum AFP were observed in any of the patients, and B-hCG was elevated in only 4 of the 47 cases. In 2 of the 4 cases, elevations of the serum B-hCG were associated with pregnancy and in the remaining 2 cases the serum CEA value was also elevated. Contrary to a study reported by other investigators, our data indicate the the tumor marker profile consisting of CEA, AFP, and B-hCG does not increase the incidence of abnormal findings when compared to the CEA test used alone. Also, our CEA data are consistent with other reports which demonstrate that CEA may be a useful tumor marker in 23% of the patients with Stage I and II disease, 57% of the patients with Stage III disease, and 33% of patients with Stage IV disease. The serum CEA test does not appear to be useful for the early detection of noninvasive (in situ) disease.     

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.     

Squamous cell carcinoma of the cervix metastatic to the heart

An unusual case of squamous cell carcinoma of the cervix in a 33 year old with metastases to the right ventricle is presented. The infrequency of this finding is supported by autopsy data from the literature. The postulated mechanisms of spread, clinical presentations, and diagnostic methods of genital malignancies to the heart are discussed.     

Characterization of tumor-associated antigen from human carcinoma of the uterine cervix

In vitro demonstration of cell-mediated immune responses to tumor-associated antigen (TAA) was observed with autologous tumor extracts from patients with cervical cancer. Seventy-six percent of these patients exhibited an inhibitory effect with autologous antigens while 59% reacted with homologous antigens. A progressive rise in percentage inhibitory activity was associated with increasing stage of the disease. The physicochemical and immunochemical characterization of the TAA found on the membrane of cervical tumor cells suggested that it may be a lipid-protein complex containing an enzyme having immunological determinants such as those of term-placental alkaline phosphatase enzyme.     

Erythropoietin receptor expression in biopsy specimens from patients with uterine cervix squamous cell carcinoma

Hypoxia, an important mechanism of radioresistance, is a strong stimulus for erythropoietin (EPO) production. The stimulatory effects of EPO are mediated through the activation of its receptors, EPO receptors (EPORs). The objective of this study is to determine whether EPORs are expressed in biopsy specimens of patients with squamous cell carcinoma of the cervix. Eighteen biopsy specimens were studied after obtaining Institutional Review Board-approved consent. Standard immunohistochemistry techniques were utilized. Expression of EPORs was present in 16 out of 18 (88.9%) specimens. The intensity (qualitative) and the frequency (semiquantitative) of EPORs expression showed a statistically significant correlation (P= 0.00379). Statistical analysis was performed to determine whether EPORs expression is related to other parameters such as age, FIGO stage, histologic grade, and hemoglobin levels. Only age showed a statistically significant correlation with EPORs frequency of expression (P= 0.00878). Currently, work is in progress in our laboratory to study the radiobiologic effects of EPO on the radiation response of cultured cancer cell lines in vitro.