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.     

Comparison between squamous cell carcinoma-associated antigen and CA-125 in patients with carcinoma of the cervix

Serum levels of CA-125 and squamous cell carcinoma-associated antigen (SCC) were measured in 30 patients with squamous cell carcinoma and 12 patients with adenocarcinoma of the uterine cervix. SCC was elevated in 67% of patients with squamous cell carcinoma but in only 25% of patients with adenocarcinoma. In contrast, CA-125 was elevated in 75% of patients with adenocarcinoma but in only 26% of patients with squamous cell carcinoma. These data demonstrate the applicability of the measurement of CA-125 as a tumor marker for cervical adenocarcinoma and confirm the value of the measurement of SCC antigen in patients with cervical squamous cell carcinoma. Moreover, we show that measurement of SCC antigen in adenocarcinoma and measurement of CA-125 in squamous cell carcinoma are of insufficient clinical value.     

Clinical significance of combined use of macrophage colony-stimulating factor and squamous cell carcinoma antigen as a selective diagnostic marker for squamous cell carcinoma arising in mature cystic teratoma of the ovary

OBJECTIVES: Mature cystic teratoma of the ovary transforms into malignant tumors, mostly squamous cell carcinomas, at an incidence of approximately 2%. Preoperative diagnosis of squamous cell carcinoma arising in mature cystic teratoma of the ovary is a difficult task. The present study aims to assess whether combined use of two serum tumor markers, macrophage colony-stimulating factor (M-CSF) and squamous cell carcinoma antigen (SCC), is effective in preoperatively diagnosing squamous cell carcinoma arising in mature cystic teratoma of the ovary, distinguishing it from mature cystic teratoma without malignant transformation. METHODS: Serum levels of M-CSF and SCC were assayed using blood samples collected preoperatively from 31 patients with squamous cell carcinoma arising in mature cystic teratoma of the ovary and 133 patients with mature cystic teratoma of the ovary without malignant transformation. RESULTS: In 22 of the 31 (71.0%) patients with squamous cell carcinoma arising in mature cystic teratoma of the ovary, the serum M-CSF levels exceeded the upper limit of the normal level (1056 U/ml). This positive incidence of the elevated serum M-CSF levels was significantly higher compared with that (13.5%, 18/133) observed in patients with benign cystic teratoma of the ovary (P < 0.0001). Regarding the serum levels of SCC, 13 of 31 (41.9%) patients with malignant tumors showed positive values exceeding the cutoff value of 2.0 ng/ml. Again, this incidence of positive cases was significantly higher compared with that (15.0%, 20/133) observed in patients with benign tumors (P < 0.01). There was no correlation between the serum levels of M-CSF and SCC among patients with squamous cell carcinoma arising in mature cystic teratoma of the ovary. Patients with malignant tumors testing positive for elevated M-CSF did not necessarily test positive for SCC. Patients with positive values for excess M-CSF and/or SCC constituted 87.1% of the total (27/31). Even when patients were restricted to those with stage I tumors, a value as high as 83.3% (15/18) was still obtained for those testing positive for elevated M-CSF and/or SCC. CONCLUSION: Serum M-CSF was proven to be useful as a tumor marker for detecting squamous cell carcinoma arising in mature cystic teratoma of the ovary. Combined use of serum M-CSF and SCC as a marker seemed to be useful in the selective diagnosis of mature cystic teratoma of the ovary harboring malignant squamous carcinoma, discriminating it from that without malignant carcinoma.     

Raised serum squamous cell carcinoma antigen levels in malignant transformation of mature cystic ovarian teratoma

Mature cystic ovarian teratoma with malignant transformation to squamous cell carcinoma was diagnosed in four patients. Squamous cell carcinoma (SCC) antigen serum levels were elevated at diagnosis and during progression of the disease, but normal in complete remission. Elevated serum SCC antigen levels were also found in four out of 19 patients with mature cystic teratoma of the ovary. Cystic fluid from mature cystic teratoma could contain very high levels of the SCC antigen (> 1000 µg l⁻¹) without any sign of malignant transformation.     

Angiogenesis in cervical intraepithelial neoplasia and early-staged uterine cervical squamous cell carcinoma: clinical significance

The objective of this study is to evaluate angiogenesis in cervical intraepithelial neoplasia (CIN), microinvasive squamous cell carcinoma (MIC), and early-staged squamous cell carcinoma (SCC), stage IB-IIA of the cervix. Microvessel density (MVD) was evaluated and correlated with other pathologic prognostic factors and disease outcomes. Four hundred seventy-four cervical specimens were studied. Among these, 100 were designated normal cervix, 30 CIN1, 32 CIN2, 178 CIN3, 74 MIC, and 60 early-staged SCC. MVD per high-power field (x400) of early-staged SCC, MIC, and CIN3 were significantly higher in comparison to CIN2, CIN1, and control subjects (P<0.05). There was no statistically significant difference in MVD between control group, CIN1, and CIN2. In early-staged SCC, no correlation between MVD and pelvic lymph node status, parametrial involvement, depth of stromal invasion, and lymphovascular space invasion was found. Patients with bad outcomes (recurrence or death) showed no statistically different MVD from the ones who had unremarkable clinical courses.     

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.     

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.     

宫颈癌前病变与宫颈鳞癌组织中Foxp3的表达及临床意义

目的 观察宫颈鳞癌及癌前病变组织中Foxp3的表达情况.方法 采用免疫组化检测浸润性宫颈鳞癌(FIGOⅠ期或ⅡA期,共20例)、宫颈上皮内瘤样病变(CIN1、CIN2、CIN3各20例)、宫颈HPV感染(20例)及正常宫颈(20例)组织中Foxp3的表达情况.结果 浸润性宫颈鳞癌与CIN3患者宫颈组织中Foxp3表达明...     

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.     

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.     

Serum squamous cell carcinoma antigen levels in patients with invasive squamous vulvar and vaginal cancer: a preliminary report

Pretreatment serum squamous cell carcinoma antigen (SCC) levels were obtained in 12 patients with invasive vulvar and 5 patients with invasive vaginal squamous cancer. Only 4 of 12 (33%) patients with vulvar cancer and 1 of 5 (20%) patients with vaginal cancer, usually those with more advanced disease, had elevated serum SCC levels at the time of diagnosis.     

A significant elevation of plasma level of matrix metalloproteinase-9 in patients with high-grade intraepithelial neoplasia and early squamous cell carcinoma of the uterine cervix

The objective of this article is to study the correlation between plasma levels of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) and multisteps of cervical carcinogenesis as well as to evaluate their clinical application. Two hundred one blood samples were collected from 52 patients with early cervical squamous cell carcinoma (SCC), 41 with high-grade cervical intraepithelial neoplasia (CIN), 27 with low-grade CIN, and 81 healthy individuals. Enzyme-linked immunosorbent assay was used to detect plasma MMP-2 and MMP-9 concentrations. Gelatin zymography was used to directly compare the activities of MMP-2 and MMP-9 and to measure the MMP-9:MMP-2 ratio. A receiver-operating characteristic curve was plotted to determine the plasma cutoff levels of these biomarkers. Patients with low- and high-grade CIN were found to have significantly different plasma MMP-9 levels (P < .001) but not MMP-2 levels. The cutoff values of 103.8 ng/mL for plasma MMP-9 and 0.70 for the MMP-9:MMP-2 ratio were used to distinguish SCC and high-grade CIN from low-grade CIN and healthy cases. The sensitivities and negative predictive values of these cutoff points were high (75.6% and 75.8% for MMP-9; 79.6% and 79.8% for the MMP-9:MMP-2 ratio). A significant elevation of plasma MMP-9 levels and the MMP-9:MMP-2 ratio in high-grade CIN and SCC patients manifests a stage point of high-grade CIN in cervical carcinogenesis and can be used as additional molecular information. Once plasma MMP-9 levels fall below 103.8 ng/mL or the MMP-9:MMP-2 ratio falls below 0.70, patients have only about a 20% chance of developing these cervical lesions.     

Significance of serum SCC antigen as a tumor marker in patients with squamous cell carcinoma of the vulva

The significance of serum SCC antigen as a tumor marker was investigated in 94 women with squamous cell carcinoma of the vulva. The incidence of elevated serum SCC levels varied from 10% in FIGO stage I to 40% in FIGO stage IV. We did not observe a correlation between elevated pretreatment SCC values and the presence of lymph node metastases. During follow-up, elevated serum SCC values were observed in 8 of 19 patients (42%) with recurrent or progressive disease. It is concluded that the determination of serum SCC levels does not provide additional information in the staging of squamous cell vulvar carcinoma, but can be useful for the early detection of recurrent disease during follow-up in some patients. However, elevated serum SCC levels were also found in 25% of patients without demonstrable tumor activity during follow-up and benign skin disorders were recognized as a cause of false-positive SCC results.     

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%.     

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 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.     

半乳凝素-3在宫颈上皮内瘤变及宫颈鳞状细胞癌中的表达及其意义

目的:探讨半乳凝素-3(Galectin-3)在宫颈上皮内瘤变(CIN)及宫颈鳞状细胞癌(SCC)中的表达及其意义。方法:选择经病理确诊为CIN和SCC患者的石蜡标本60例,以同时期因子宫肌瘤行全子宫切除患者的正常宫颈组织(NC)石蜡标本10例作为对照,采用免疫组化方法分析CIN及SCC中Galectin-3表达情况。结果:NC、CIN、SCC及SCCⅠ、SCCⅡ、SCCⅢ组Galectin-3表达阳性率分别为40.00%、50.00%、83.33%及70.00%、90.00%、90.00%。NC、CIN、SCC3组间Galectin-3表达阳性率差异有统计学意义(χ2=9.559,P=0.049);NC组Galectin-3表达阳性率与SCCⅡ期组及Ⅲ期组比较,差异有统计学意义(χ2=5.495,P=0.029)。宫颈肿瘤>2cm组Galectin-3表达阳性率高于≤2cm组,差异有统计学意义(χ2=4.690,P=0.047)。结论:SCC中Galectin-3的阳性表达与肿瘤大小有关;Galectin-3表达阳性率随宫颈病变发展而升高。Galectin-3可能在SCC的发生、进展中发挥作用。     

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.     

A comparison of pretreatment serum levels of four tumor markers in patients with endometrial and cervical carcinoma

CA125 (reference value [RV] = 35 U/mL), CA50 (RV = 20 U/mL), CA72.4 (RV = 3.8 U/mL) and SCC (RV = 3.6 ng/mL) levels were retrospectively assayed in blood samples collected at diagnosis from 42 patients with endometrial carcinoma, 45 patients with cervical carcinoma and 68 patients with benign uterine pathology as controls. Among the patients with endometrial carcinoma. CA50 was the antigen with the highest sensitivity (SE) (34.4%) followed by CA125 (26.2%), CA72.4 (21.9%) and SCC (16.7%). The incidence of elevated serum CA125 and CA72.4 levels was significantly greater in advanced stages than in early ones (66.7% vs 19.4%, p = 0.032 for CA125; 66.7% vs 11.5%, p = 0.012 for CA72.4), while CA50 positivity was not significantly correlated with the extent of disease (50% in advanced stages vs 30.8% in early ones, p = 0.38). Among the patients with cervical carcinoma, CA125 and CA50 respectively showed a SE of 33.3% and of 42.9% for adenocarcinoma, while SCC had a SE of 33.3% and of 42.9% for squamous cell adenocarcinoma; in particular among the patients with squamous cell carcinoma, the incidence of elevated SCC levels was correlated with the extent of tumor (57.1% in advanced stages vs 12.5% in early ones, p = 0.013). In conclusion, CA50 and CA125 were the most sensitive tumor markers in both endometrial carcinoma and cervical adenocarcinoma, while SCC was the most reliable antigen for squamous cell carcinoma of the cervix. Because of the affinity of SCC, CA50 and CA125 for different histological types of cervical carcinoma, the combined evaluation of SCC with CA50 or CA125 showed an increased SE with respect to each marker alone.     

Cyclooxygenase-2 expression in cervical intraepithelial neoplasia III and squamous cell cervical carcinoma, and its correlation with clinicopathologic variables

The objective of the study was to compare cyclooxygenase-2 (COX-2) expression in cervical intraepithelial neoplasia III (CIN III) and squamous cell carcinoma (SCC) of the cervix, and its correlation with clinicopathologic factors of SCC with a review of the available literature. This study included 25 patients with CIN III and 67 patients with stage I-IIa SCC. All patients in the SCC group were treated with radical hysterectomy plus pelvic and para-aortic lymphadenectomy and postoperative chemoradiotherapy based on their histopathologic risk factors. Immunohistochemical analysis was performed on paraffin-embedded sections with COX-2 antibody. COX-2 expression in the SCC group was significantly higher than in the CIN III group (55.2% [37/67] vs 24% [6/25]; P= 0.008). Significantly higher expression of COX-2 was observed in patients with lymphovascular space invasion (LVSI) compared to patients without LVSI (61.9% [34/55] vs 33.3% [3/9]; P= 0.02). Additionally, patients with tumor sizes >4 cm had significantly higher COX-2 expression than patients with tumor sizes <4 cm (65.9% [27/41] vs 39% [10/26] P= 0.028). There was no significant relationship with respect to COX-2 expression and parametrial involvement, lymph node metastasis, recurrences, and survival. In multivariate analysis, LVSI was the only statistically significant determinant for COX-2 expression (P= 0.024; OR = 2.35; 95% CI = 1.1-4.9). Our results and a review of the literature both suggest that COX-2 expression may have a role in the development and progression of CIN III and it is related to some clinicopathologic variables of cervical carcinoma. Further studies are needed to clarify the role of COX-2 inhibitors in the management of CIN and SCC.