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%.     

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.     

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。     

Local immune response in squamous cell carcinoma of the uterine cervix

The role of Langerhans cells as antigen-presenting cells was examined in cervical carcinomas. Frozen samples were obtained from 34 women with stage Ib and II cervical carcinomas. Langerhans cells (CD1), T lymphocytes (CD4 and CD8), B lymphocytes (CD22), and natural killer (CD57, NK) cells were all quantitatively assessed in cervical carcinomas using immunohistochemical methods. These results were related to the MHC class I and II expression on the tumor cells. The majority of Langerhans cells were distributed among cancer cells and they were positively correlated with CD4+, NK and B cells in cervical carcinomas. This is suggestive of the presence of local immune response. The numbers of Langerhans, CD4+, CD8+ and NK cells did not significantly correlate with age at operation, lymph node metastases or depth of cervical wall invasion. The downregulation of MHC class I expression found in 8 (24%) carcinomas was not associated with the decrease in the number of immunologic cells. The upregulation of MHC class II expression found in 26 (76%) carcinomas was significantly associated with the increase in the number of Langerhans cells (p < 0.007). However, the association between the upregulation of MHC-II expression and CD4+ cells did not reach statistical significance (p < 0.07). This is probably due to a small case in this study. MHC-II-restricted immunity may partly contribute to the local immune response in stages Ib and II squamous cell carcinoma of the uterine cervix.     

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.     

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。     

Galectin-7 levels predict radiation response in squamous cell carcinoma of the cervix

Objective

We previously found that galectin-7 was upregulated in patients with cervical cancer who remained recurrence-free after chemoradiation. We hypothesized that pretreatment levels of galectin-7 predict radiation response in patients with squamous cell carcinoma (SCC) of the cervix.

Methods

Galectin-7 expression was assessed by immunohistochemical staining of a tissue microarray of paraffin-embedded specimens from 161 patients with cervical SCC treated with definitive radiation therapy in 1980–1999. Galectin-7 expression was scored as absent or present. Distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were computed using the Kaplan–Meier method and log-rank tests.

Results

The median age at diagnosis was 45 years (range 21–85) and median follow-up interval was 71 months (range 0–285). Of the 161 patients, 105 (65%) had FIGO stage IB disease, 18 (11%) stage IIA, and 38 (24%) stage IIB. Median tumor diameter was 5.5 cm (range 3.5–8). Seven patients (4%) received concurrent chemotherapy; 139 patients (86%) had galectin-7-positive tumors and 22 (14%) galectin-7-negative tumors. Five-year DMFS rates for patients with galectin-7-positive versus -negative tumors were 73% and 55% (p = 0.05); DSS, 65% and 36% (p = 0.004); and OS, 64% and 36% (p = 0.005). In multivariate analysis adjusting for age, stage, and tumor diameter, galectin-7 expression remained a significant predictor of DMFS (hazard ratio [HR] = 0.43, p = 0.03), DSS (HR = 0.34, p = 0.001), and OS (HR = 0.34, p = 0.001).

Conclusions

Elevated galectin-7 expression is associated with improved outcomes after radiation therapy for cervical cancer. Further studies are required to validate these findings and clarify the role of galectin-7 in disease progression and radiation response.     

Chemotherapy of squamous cell carcinoma of the cervix

Four cases of recurrent squamous cell carcinoma of the cervix were treated with a combination of bleomycin and mitomycin C. There was a complete tumor response in at least 2 of the patients treated. Response is well documented with an external tumor marker visible on 1 patient.     

The treatment of microinvasive squamous cell carcinoma of the uterine cervix.

Between 1947 and 1971 254 cases of microinvasive carcinoma of the uterine cervix were treated in this institution. Cervical cytology was used to detect the cervical abnormality and the diagnosis of microinvasion was established by cone biopsy. During this time period microinvasion was defined as the breakthrough of the basement membrane and the penetration of neoplastic epithelium into the stroma to a depth of no greater than 5 mm, and excluded those cases which had lymph or blood vessel involvement, a dentritic or staghorn pattern, many epithelial cells in clusters in the stroma, or the presence of confluence. Of the 254 cases, 250 were followed for 5 years or more. Treatment methods for microinvasive cervical cancer over this time period included surgery alone, radiotherapy alone, or a combined approach using both surgery and radiotherapy. None of the 125 cases treated by surgery alone have died of cervical cancer. It is concluded that microinvasive carcinoma, as defined in this study, can be cured by conservative surgical means.     

Concurrent radiotherapy with paclitaxel/carboplatin chemotherapy as a definitive treatment for squamous cell carcinoma of the uterine cervix

OBJECTIVES: To evaluate the toxicity and the efficacy of paclitaxel/carboplatin chemoradiotherapy as a definitive treatment for squamous cell cancer of the uterine cervix. METHODS: From March 2000 to January 2004, 33 patients with squamous cell cancer of the uterine cervix were treated with concurrent chemoradiotherapy including 2 cycles of paclitaxel (135 mg/m(2)) and carboplatin (area under the time-concentration curve 4.5 mg min/ml) at 4-week interval. Seven patients received adjuvant chemotherapy with the same chemotherapeutic regimen. All patients received external beam radiotherapy with 41.4-51.4 Gy (median 50.4 Gy) to the whole pelvis. Twenty-eight patients received boost irradiation to the cervix by brachytherapy with 25.6-43.3 Gy (median 34.6 Gy) and 5 patients by external beam radiotherapy with 10.8-14.4 Gy (median 14.4 Gy). RESULTS: A median follow-up period was 27 months (range: 6-53 months). Acute hematological toxicity of grade 3 or 4 developed in 20 patients (61%), and acute gastrointestinal toxicity of grade 3 developed in 1 patient (3%). Vesicovaginal fistula occurred in 2 patients (6%). All patients achieved objective response (CR 70%, PR 30%) in 2 months after termination of treatment. One patient had a local progression in cervix, and 4 patients developed distant metastases. The 3-year estimated disease-free survival rates for stages I-IIA, IIB, III and IV were 67%, 91%, 88% and 50%, respectively. The 3-year estimated survival rates for stages I-IIA, IIB, III and IV were 89%, 91%, 88% and 50%, respectively. CONCLUSION: Concurrent chemoradiotherapy with paclitaxel and carboplatin is effective to achieve an excellent pelvic control.     

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.     

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.     

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.     

Scalp metastasis from squamous cell carcinoma of the cervix

Abstract. Maheshwari GK, Baboo HA, Ashwathkumar R, Dave KS, Wadhwa MK. Scalp metastasis from squamous cell carcinoma of the cervix.
We describe a 45-year-old woman with squamous cell carcinoma of the cervix stage IIB, who was initially treated with radical radiotherapy. The patient developed multiple scalp metastases 8 months following her treatment. The scalp was involved in the disease as the sole anatomic site of distant cutaneous metastasis. The scalp lesions were treated with palliative radiotherapy. A search of the literature revealed only two cases of such distant metastatic involvement of the scalp from cervical cancer.     

Pigmented squamous cell carcinoma of the uterine cervix.

A 57-year-old female presented with an abnormal Pap smear. Colposcopic examination of the cervix revealed white mucosa with erosion and several areas of black pigmentation. After a colposcopically directed biopsy and loop conization, radical hysterectomy and bilateral salpingo-oophorectomy with pelvic and paraaortic lymphadenectomy were performed. Pathological examination disclosed an invasive squamous cell carcinoma admixed with many dendritic melanocytes. Melanin granules were present within the melanocytes and tumor cells. Although similar tumors have been reported in other sites, this is the first report to our knowledge of a pigmented squamous cell carcinoma of the uterine cervix.     

Superficially invasive squamous cell carcinoma of the cervix.

The microscopic pathologic features of early invasive squamous cell cervical carcinoma are used as determinants for the treatment of these lesions. This study is a retrospective review of 180 patients with squamous cell cervical carcinoma with invasion to a depth of 5 mm or less. Invasion of less than or equal to 1 mm, greater than 1 but less than or equal to 3 mm, greater than 3 but less than or equal to 5 mm was noted in 37, 84, and 59 patients, respectively. The median follow-up was 6.5 years. Four (2.2%) patients developed carcinoma in situ of the vagina and four (2.2%) patients progressed to invasive squamous carcinoma. Pelvic lymph node metastases were rare (1%). No patient has died from recurrent disease. Analysis of numerous clinical and pathological variables identified no risk factors for recurrence. Most (54/68) patients with tumor invading beyond 3 mm or with tumor demonstrating vascular invasion were treated by traditional "radical" methods. This limited a meaningful analysis of the risk of conservative treatment. The reliability of using the existing definitions of microinvasive disease for the guidance of treatment remains controversial. Further clarification may be rendered only with prospective clinical-pathologic studies performed by cooperative groups.