Elevated Serum Squamous Cell Carcinoma Antigen Research Articles

Abstract 2374: Squamous cell carcinoma antigen regulates macrophage polarization, contributing to inhibition of T cell activity in cervical cancer chemo-radiotherapy

Abstract Chemoradiation therapy (CRT) is the standard treatment for locally advanced cervical cancer. Anti-tumor T cell response is critical for immunogenic cell death and tumor regression enabled by CRT. Squamous cell carcinoma antigen (SCCA) is highly expressed in cervical tumors and passively released from tumor cells. Patients with elevated serum SCCA often showed radioresistance and recurrence. Despite its prognostic value, little is known about the function of extracellular SCCA. We analyzed SCCA-associated immune landscape using RNAseq from 20 cervical matched tumor biopsy pairs collected prior to (pre-) and 3 weeks into (mid-) CRT. Patients with low pretreatment SCCA (<6 ng/ml, SCCA/L) and high SCCA (≥6ng/ml, SCCA/H) showed decreased CD4/CD8 T cells at mid-CRT, with a more significant decrease in SCCA/H patients. This corresponded to significantly reduced expression of T-cell trafficking chemokine CXCL9/10 during CRT, particularly in SCCA/H patients. Interestingly, granzyme B (GZMB) and interferon-γ (IFNγ), associated with T-cell cytotoxicity, were increased in 6 of the 10 SCCA/L patients, compared to 1 and 2 of the 10 SCCA/H patients with increased GZMB and IFNγ respectively. Another RNAseq cohort of 66 pre-CRT tumor biopsies also showed significantly higher LAG3 and CTLA4 expression in SCCA/H than SCCA/L patients. In vitro stimulation of human PBMC with CD3/28 antibody in the presence of SCCA1 protein resulted in inhibition of T cell proliferation and decreased cytotoxicity. However, when SCCA1 was incubated with purified CD3 T cells, no inhibition in T cell activity was observed, suggesting the involvement of myeloid cells in SCCA1 mediated T cell activity. To investigate the effect of SCCA1 on myeloid cells, we isolated human CD14+ monocytes, incubated with SCCA1, and found improved survival of CD14+ HLADRlo/neg monocytes. THP1 monocytes, possessed polarizing ability, were differentiated into M1/M2 macrophage with the supplement of SCCA1 during the polarization. The result showed that SCCA1 promoted M2 macrophage phenotypes, including increased M2 marker (CD209), PD-L1 expression, M2-associated cytokines (IL10, CCL18), and M2 polarizing signaling (STAT3 phosphorylation and Myc expression). Macrophages isolated from murine tumors with high SCCA1 expression demonstrated increased suppression on T cell activity in co-culture functional assays. Furthermore, tissue microarray from cervical cancer patients showed that high SCCA was associated with increased infiltration of CD11b+ myeloid cells and CD68+ macrophages in tumors. Overall, we concluded that SCCA promoted M2 polarization and macrophage infiltration, which may contribute to T cell exhaustion, leading to poor survival. Thus, therapeutic targeting of extracellular SCCA should be considered to improve treatment outcomes. Citation Format: Liyun Chen, Victoria Shi, Matthew Inkman, Jin Zhang, Pippa Cosper, Julie K. Schwarz, Stephanie Markovina. Squamous cell carcinoma antigen regulates macrophage polarization, contributing to inhibition of T cell activity in cervical cancer chemo-radiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2374.

Clinical Significance of Serum Squamous Cell Carcinoma Antigen for Patients with Recurrent Esophageal Squamous Cell Carcinoma.

Squamous cell carcinoma antigen (SCC-Ag) is a widely used tumor marker of SCC. However, the clinical significance of serum SCC-Ag levels in recurrent esophageal SCC (ESCC) remains unclear. This study aimed to investigate the clinical relevance of serum SCC-Ag levels in patients with recurrent ESCC after surgery. This study retrospectively analyzed 208 patients who experienced recurrence after curative resection for ESCC. Serum SCC-Ag levels at the time of recurrence were collected from the patients' records. The patients were classified into tertiles based on the serum SCC-Ag values (low, middle, and high), and the clinical characteristics and outcomes were compared among the groups. Significant differences in sex (p = 0.001), pathologic T (p = 0.034), and N stages of primary cancer (p = 0.015) were observed among the groups. Although the recurrence patterns did not differ significantly, a high SCC-Ag was significantly associated with multiple recurrences (p = 0.019). The high-SCC-Ag group patients demonstrated a shorter time to recurrence than the other groups (p = 0.044). The SCC-Ag levels were significantly associated with overall survival after recurrence (p = 0.036). Multivariate analysis showed that serum SCC-Ag value at recurrence was an independent poor prognosticator (p = 0.031). Elevated serum SCC-Ag levels at recurrence were significantly associated with a reduced time to recurrence, multiple recurrences, and a poor prognosis after recurrence. An alternative to the current standard treatment is required to improve the outcome for patients with high serum SCC-Ag levels at recurrence.

Could Adjuvant Chemotherapy Improve Prognosis for Cervical Cancer Patients with Elevated Pretreatment Serum Squamous-Cell Carcinoma Antigen?

ObjectiveThe aim of this study was to explore whether adjuvant chemotherapy could improve prognosis for cervical cancer patients with elevated pretreatment serum squamous-cell carcinoma antigen (SCC-Ag).MethodsPropensity-score matching and inverse probability of treatment weighting (IPTW) were used to ensure balanced groups for patients with (arm A) and without adjuvant chemotherapy (arm B). All patients were treated between January 2012 and December 2014 at a single center. Study outcomes were disease-free survival (DFS) and overall survival (OS).ResultsIn total, 81 patients were included in this study. By propensity-score matching, 35 patients were included in each group (arm A and arm B). Median follow-up was 60 months in arm A and 66 months in arm B. Overall, 85.7% of patients in arm A and 71.4% of those in arm B received adjuvant radiotherapy. DFS and OS curves were similar between arms A and B (P=0.971 and 0.633, respectively). With IPTW, arm A was not associated with prognosis in terms of DFS (HR 0.946, 95% CI 0.237–3.784; P=0.938) or OS (HR 1.020, 95%CI 0.357–2.913; P=0.970).ConclusionFor patients with elevated pretreatment SCC-Ag, adjuvant chemotherapy was not found to improve prognosis. Also, a considerable proportion of these patients had postoperative indications for adjuvant radiotherapy. For these cervical cancer patients with elevated pretreatment SCC-Ag, the choice of radical hysterectomy and adjuvant chemotherapy should be prudent.

Abstract 2426: SERPINB3 promotes radiation resistance in cervical cancer by inhibiting lysosome-mediated cell death

Abstract The purpose of this study was to determine if squamous cell carcinoma antigen (SCCA), also known as SERPINB3, protects cervical cancer cells from ionizing radiation (IR)-induced death, and to determine the mechanism(s) of IR-induced cell death with or without SERPINB3. Cervical cancer remains a leading cause of cancer death in women worldwide despite advances in screening, vaccination and treatment. Recurrence after definitive chemoradiation occurs in up to 30-50% of patients with locally advanced disease. We and others have demonstrated that elevated serum SCCA portends poor prognosis in cervical cancer. In addition, CRISPR-Cas9-mediated knock out of SERPINB3 significantly sensitizes cervical tumor cells to IR in vitro. We hypothesize that SERPINB3 promotes radioresistance by protecting cells against lysosome damage and lysosomal mediated necrosis. Two cervical cancer cell lines with high SERPINB3 expression were edited using CRISPR-Cas9 technology at the SERPINB3 locus resulting in knock out (KO). B3-KO cells were significantly more radiation sensitive compared to control cells at all doses and time points evaluated. Cell death morphology in the B3-KO cells was necrotic, with large cytoplasmic single membraned vesicles, many of which were ruptured, consistent with that seen in lysosome-mediated necrosis. Live-cell time-lapse imaging showed loss of lysosome integrity in the hours leading up to cell death (propidium iodide nuclear staining). Western blot analysis showed low levels of caspase-3 and caspase-7 cleavage only at high doses and late time points after IR, with no evidence of phospho-MLKL or phospo-RIPK3 (markers of necroptosis), or gasdermin-D cleavage (marker of pyroptosis). Necrostatin, ferrostatin, liproxstatin and YVAD-Cho had little to no effect on cell death following IR, while pan-caspase inhibitors decreased IR-induced cell death in both control and B3-KO cells, and E64D decreased IR-induced cell death in B3-KO cells to a greater degree than control cells. Additionally, cervical tumor cell lines that had no detectable expression of SERPINB3 were engineered to expressed high levels of SERPINB3 (B3-wt) or SERPINB3 containing the P14 mutation A351R (B3-P14m), which lacks protease inhibitory function. B3-wt expressing cells displayed increased radiation resistance in clonogenic survival assays and mouse tumor models. Growth rate and radiation response of B3-p14m expressing tumors was similar to vector control. These data suggest that SERPINB3 is an important mediator of radiation response in cervical cancer and protects cells by inhibiting cysteine protease-dependent cell death, likely via lysosome-mediated necrosis. These findings support SERPINB3 as a potential target for novel radiosensitizing therapies. Citation Format: Songyan Wang, Clifford Luke, Victoria Shi, Perry Grigsby, Gary Silverman, Stephanie Markovina. SERPINB3 promotes radiation resistance in cervical cancer by inhibiting lysosome-mediated cell death [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2426.

Assessment of the relationship between serum squamous cell carcinoma antigen (SCC-Ag) concentration in patients with locally advanced squamous cell carcinoma of the uterine cervix and the risk of relapse.

IntroductionParameters that will help to identify patients with better and worse prognosis are sought in subjects with locally advanced squamous cell cervical carcinoma.Aim of the studyTo assess the relationship between squamous cell carcinoma antigen (SCC-Ag) concentration and the risk of relapse in patients with squamous cell cervical carcinoma staged IIB-IIIB.Material and methodsThe study group consisted of 52 patients with cervical squamous cell carcinoma staged II B (n = 39) and IIIB (n = 13). Serum SCC-Ag concentration was assessed prior to radiochemotherapy or radiotherapy and four weeks after treatment.ResultsThe follow-up after treatment ranged from 1 to 33 months (16.2 ±10.5). During follow-up, nine relapses were diagnosed (17.3%). The concentration of SCC-Ag before the treatment was elevated in 41 cases (78.8%) and in 11 cases (21.2%) it was ≤ 2 ng/ml. In all the patients with relapses SCC-Ag concentration before the treatment was elevated. Relapses were diagnosed in five patients with elevated SCC-Ag concentration after the treatment (55.6%) and in four patients with normal SCC-Ag concentration after the treatment (9.3%). There was a positive correlation between SCC-Ag concentration before and after the treatment and relapse occurrence.ConclusionsEvaluation of serum SCC-Ag concentration in patients with locally advanced squamous cell cervical carcinoma before treatment is a valuable supplementary diagnostic tool and patients with high SCC-Ag concentration are at an increased risk of relapse. Due to the relationship between elevated serum SCC-Ag concentration after treatment and increased risk of relapse, these patients may require a more intensive post-treatment follow-up.

Complementary Roles of Squamous Cell Carcinoma Antigen and 18F-FDG PET/CT in Suspected Recurrence of Cervical Squamous Cell Cancer

Purpose: To assess the clinical value of FDG PET/CT and evaluate the complementary roles of serum squamous cell carcinoma antigen (SCCAg) and FDG PET/CT in the diagnosis of suspected recurrent of cervical squamous cell cancer. Methods: Serum SCCAg levels were retrospectively reviewed in patients previously treated for cervical squamous cell carcinoma, who had suspected recurrence of cervical cancer and who had undergone FDG PET/CT scans. The clinical impact of elevated SCCAg (>1.5 ng/ml) and negative SCCAg (≤1.5 ng/ml) levels were analyzed based on the results of PET/CT and final diagnosis. Results: The overall patient-based sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of PET/CT for the detection of tumor recurrence or malignancy were 100% (86/86), 80.8% (21/26), 95.5% (107/112), 94.5% (86/91) and 100% (21/21), respectively. Of the 112 patients included in this study, recurrence or malignancy was detected by PET/CT in 62 of the 64 patients with elevated SCCAg, compared to 24 of the 48 patients with negative SCCAg levels. The overall patient-based PPV, NPV, sensitivity and accuracy of SCCAg for the detection of tumor recurrence or malignancy were 96.9% (62/64), 50% (24/48), 72.1% (62/86) and 76.8% (86/112), respectively. The five false-positive PET/CT results were all associated with patients with negative SCCAg levels. The PPV of positive PET/CT-associated elevated SCCAg for the detection of tumor recurrence or malignancy was 100% (62/62). The NPV of negative SCCAg-associated negative PET/CT was 100% (19/19). Conclusions: Serum SCCAg evaluation and FDG PET/CT imaging can be complementary techniques in cases of suspected recurrent cervical squamous cancer. Positive PET/CT with elevated SCCAg can predict recurrence. Although PET/CT cannot confidently be deferred due to a negative SCCAg test, the possibility of a false-positive PET/CT in those cases may have diagnostic importance.

Squamous cell carcinoma antigen

The objective of this retrospective study was to investigate the predictive value of pretreatment serum squamous cell carcinoma antigen (SCCAg) levels in 174 patients with squamous cell carcinoma of the anus who received concurrent chemoradiation between 1997 and 2010. Pretreatment serum SCCAg measurements in patients with histologically diagnosed squamous cell carcinoma of the anal canal and margin who received chemoradiation were compared with clinical tumor classification and lymph node status for prognostic/predictive ability, including 1) tumor response after the completion of chemoradiation treatment, 2) disease recurrence, and 3) overall survival. Clinical measurements and scores were compared using Spearman rank tests, and survival was assessed in both univariate and multivariate survival analyses. The median pretreatment levels of SCCAg according to clinical tumor classification and clinical lymph node status were 0.8 μg/L in T1 tumors, 1.90 μg/L in T2 tumors, 2.5 μg/L in T3 tumors, 3.8 μg/L in T4 tumors, 1.35 μg/L in patients with N0 status, and 3.05 μg/L in patients with N0+ status (correlation coefficient: T-classification, 0.43; lymph node status, 0.38; both P < .00001). Of the patients who had normal SCCAg levels, 95% achieved a complete response after initial treatment; and, of those who had elevated SCCAg levels, 86% achieved a complete response (P = .05). Overall survival (hazard ratio, 2.5; P = .007) and disease-free survival (hazard ratio, 2.2; P = .058) were worse for those who had elevated pretreatment serum SCCAg concentrations. Pretreatment SCCAg levels in patients with squamous cell carcinoma of the anal canal and margin were correlated with clinical tumor classification and clinical lymph node status. Elevated levels of SCCAg were associated with a reduced chance of achieving a complete response and an increased chance of recurrence and death. The authors recommend further studies to determine the prognostic value of SCCAg in anal squamous cell carcinoma and suggest the potential use of SCCAg as a stratification factor in future trials.

Utility of serum squamous cell carcinoma antigen levels at the time of recurrent cervical cancer diagnosis in determining the optimal treatment choice

ObjectiveTo investigate the utility of serum squamous cell carcinoma antigen (SCC-Ag) levels upon the diagnosis of recurrent cervical cancer for decision making in patient management.MethodsClinical records from 167 cervical cancer patients who developed recurrence between April 1996 and September 2010 were reviewed. A Cox proportional hazards regression model was used to investigate the prognostic significance of serum SCC-Ag levels at the time of recurrence. The effects of various salvage treatments on survival outcomes of recurrent cervical cancer were examined with respect to serum SCC-Ag levels.ResultsSerum SCC-Ag levels were elevated (>2.0 ng/mL) in 125 patients (75%) when recurrence was diagnosed. These patients exhibited significantly shorter postrecurrence survival than those with normal SCC-Ag levels (log-rank; p=0.033). Multivariate analyses revealed that an elevated serum SCC-Ag level was an independent prognostic factor for poor postrecurrence survival. In patients with SCC-Ag levels <14.0 ng/mL, radiotherapy or surgery resulted in improved survival compared with chemotherapy or supportive care. In contrast, in patients with SCC-Ag levels of ≥14.0 ng/mL, salvage treatment with radiotherapy had only a minimal impact on postrecurrence survival.ConclusionThe serum SCC-Ag level measured when cervical cancer recurrence is diagnosed can be useful for deciding upon the appropriate salvage treatment.

Use of serum squamous cell carcinoma antigen for follow-up monitoring of cervical cancer patients who were treated by concurrent chemoradiotherapy

BackgroundTo investigate the significance of monitoring the levels of the serum squamous cell carcinoma antigen (SCC-Ag) for the detection of recurrent disease in patients with cervical cancer treated by concurrent chemoradiotherapy.MethodsThe records of 112 patients with cervical cancer were reviewed. Serum SCC-Ag levels were measured at regular follow-up visits. A SCC-Ag level of 2 ng/mL was considered the upper limit of normal. Biochemical failure was defined as two consecutively increasing SCC-Ag values above normal. Recurrent disease was confirmed by histologic and radiographic studies.ResultsEighteen patients (16%) developed recurrent disease. Sixteen patients had initially elevated SCC-Ag, post-treatment normalization of SCC-Ag, and tumor recurrence. The SCC-Ag difference (ΔSCC-Ag), defined as the difference between the last value after two consecutively increases above normal and the value immediately before the elevation, had good clinical performance in predicting cancer recurrence. The cutoff value of ΔSCC-Ag was 0.95 ng/mL.ConclusionsSCC-Ag is a relatively good method for the detection of disease recurrence in patients with cervical cancer who were treated by concurrent chemoradiotherapy.

Application of 18F-FDG PET/CT in cervical cancer with elevated levels of serum squamous cell carcinoma antigen during the follow-up

Accurate and early diagnosis of recurrence for cervical cancer after the treatment and aggressive salvage treatment could improve the prognosis of this disease. Serum squamous cell carcinoma antigen (SCCAg) is the most commonly used tumor marker for the detection of asymptomatic recurrence of cervical cancer. This study was to evaluate the application and value of (18)F-FDG PET/CT in cervical cancer with elevated of serum SCCAg level during the follow-up. Thirty-one patients with cervical cancer with elevated serum SCCAg level during the follow-up undergoing (18)F-FDG PET/CT in Sun Yat-sen University Cancer Center between August 2005 and November 2008 were entered into this retrospective study. The pathological types, the serum SCCAg level, PET/CT results, results of other imaging modalities, pathological and clinical follow-ups were recorded. All 31 patients'pathological examination showed squamous cell carcinoma, including three adenosquamous carcinoma. Lesions of all patients were examined by PET/CT. Three patients had local recurrence in the uterus or vagina, 28 had metastatic disease. Of these 31 patients, three were confirmed to have local recurrent disease, 27 were verified to have metastatic disease and one was diagnosed as primary lung squamous cell carcinoma by pathological or clinical manifestations. The total detection rate of PET/CT for malignancy was 100% (31/31); the diagnostic accuracy of PET/CT for recurrent cervical cancer was 96.8% (30/31). The levels of serum SCCAg during the follow-up were 1.5-37.8 ng/ml. There was no relation between the level of serum SCCAg and the maximum standard uptake value (SUVmax) of PET/CT. Compared with other imaging modalities, PET/CT was more efficient in detecting recurrence and finding more lesions. An elevated level of SCCAg in cervical cancer during the follow-up indicates tumor recurrence. PET/CT is efficient in detecting the recurrence and has high diagnostic accuracy.

Preoperative Serum Squamous Cell Carcinoma Antigen Levels in Clinical Decision Making for Patients With Early-Stage Cervical Cancer

To prevent morbidity associated with double modality treatment, early-stage cervical cancer patients should only be offered surgery when there is a low likelihood for adjuvant radiotherapy. We analyzed whether serum squamous cell carcinoma antigen (SCC-ag) analysis allows better preoperative identification of patients with a low likelihood for adjuvant radiotherapy than currently used clinical parameters. In a cohort study, International Federation of Gynecology and Obstetrics (FIGO) stage, tumor size, and preoperative serum SCC-ag levels, as determined by enzyme immunoassay, were related to the frequency of postoperative indications for adjuvant radiotherapy in 337 surgically treated, FIGO stage IB/IIA, squamous cell cervical cancer patients. In patients with normal preoperative SCC-ag, 16% of IB1 and 29% of IB2/IIA had postoperative indications for adjuvant radiotherapy, in contrast to 57% of IB1 and 74% of IB2/IIA patients with elevated (> 1.9 ng/mL) serum SCC-ag (P < .001). Serum SCC-ag was the only independent predictor for a postoperative indication for radiotherapy (odds ratio, 7.1; P < .001). Furthermore, in IB1 patients that did not have indications for adjuvant radiotherapy, 15% of patients with elevated preoperative serum SCC-ag levels recurred within 2 years, compared with 1.6% of patients with normal serum SCC-ag levels (P = .02). In early-stage cervical cancer, determination of serum SCC-ag levels allows more refined preoperative estimation of the likelihood for adjuvant radiotherapy than current clinical parameters, and simultaneously identifies patients at high risk for recurrence when treated with surgery only. The role of preoperative serum SCC-ag in the management of patients with early-stage cervical cancer deserves further investigation.

Positron emission tomography for unexplained serum SCC-Ag elevation during follow-up in cervical cancer patients -A phase II study

9606 Background: Serum squamous cell carcinoma antigen (SCC-Ag) elevation without detectable recurrent lesion during follow-up in cervical cancer patients presents a diagnostic and therapeutic challenge. We evaluated fluorine-18-labeled fluoro-2-deoxy-D-glucose positron emission tomography (PET) in this situation by a prospective trial. Methods: Women with cervical cancer, having completely responded to primary or salvage treatment, had serum SCC-Ag >= 2.0 ng/ml in two consecutive measures and had no evidence of recurrence detected by conventional studies were eligible. Patients with skin lesion(s), documented renal function impairment or pulmonary lesion(s) that might explain the SCC-Ag elevation were excluded. PET was undertaken within 2 weeks after conventional studies. Results: 27 consecutive patients were registered. Positive PET findings were showed in 19 patients: 14 with distant lesion(s), 2 with local lesion(s) and 3 with local and distant lesions. 17 patients with positive PET findings were confirmed to have disease recurrence and another two were free of recurrence but had severe anthracosis in the positive mediastinal nodes. 7 of the 8 patients with negative PET did not recur at follow-up. 7 patients with recurrence received curative-intended therapies and complete response was achieved in 6 patients, in whom 4 were currently alive without disease. Compared to a historical group of 30 patients with elevated SCC-Ag as the first sign of recurrence, the adding of PET reduced the usage of futile curative therapy and significantly increased patients' overall survival. Conclusions: PET expedited the detection of recurrences in patients with unexplained SCC-Ag elevation and lead to an improvement in patients' survival. No significant financial relationships to disclose.

Squamous cell carcinoma antigen: a role in the early identification of nodal metastases in men with squamous cell carcinoma of the penis.

To evaluate whether serum squamous cell carcinoma antigen (SCCAg) measurements may be of use in identifying nodal metastases in patients with SCC of the penis after treating the primary tumour. The levels of SCCAg were analysed in 11 men with penile SCC between 1994 and 2001. An elevated SCCAg level had a sensitivity of 57% (95% confidence interval, CI, 18-90%) and a specificity of 100% (CI 40-100%) for nodal metastases. Levels of SCCAg increased exponentially in patients who developed nodal metastases after treatment of the primary tumour, and were elevated before clinical or radiological evidence of nodal disease. Either the absolute level or the rate of rise of SCCAg may be a useful tool with which to follow patients after excision of the primary tumour. It may be more sensitive than computed tomography and magnetic resonance imaging in detecting recurrence, but further evaluation is needed.

Serum squamous cell carcinoma antigen and CYFRA 21-1 in cervical cancer treatment

Purpose : To analyze whether serum squamous cell carcinoma (SCC) antigen and cytokeratin-19 fragments (CYFRA) levels can assist in selecting patients with locally advanced cervical cancer who will benefit from combined treatment or additive surgery. Methods and Materials : Of 114 patients with cervical cancer Stage IB–IV, the first 39 patients received radiotherapy, the following 75 patients received identical radiotherapy plus concomitant chemotherapy (3 cycles of carboplatin and 5-fluorouracil). SCC antigen and CYFRA 21-1 serum levels were measured before treatment, after therapy, and during follow-up. Baseline tumor markers were related to tumor stage and size and clinical outcome. Results : Before treatment, SCC antigen was elevated (>1.9 μg/L) in 60% and CYFRA 21-1 (>2.2 μg/L) in 46% of patients. For all patients, disease-free survival (DFS) was better after combined treatment (67% vs. 43%, p < 0.0005). For patients with elevated baseline SCC antigen, DFS was better after combination therapy (67% vs. 27%, p = 0.001) which resulted more frequently in a normal SCC antigen (93% vs. 65%, p = 0.004). In contrast, in those with a normal baseline CYFRA 21-1, combined therapy resulted in a better DFS ( p = 0.04). Patients who achieved a normal SCC antigen or CYFRA 21-1 after treatment had a better DFS (respectively 63 vs. 17% and 64 vs. 30%). Elevated SCC antigen posttreatment indicated residual tumor in 11/12 patients (92%), elevated CYFRA 21-1 in 7/10 patients (70%). Forty-seven patients had a tumor recurrence. At recurrence, SCC antigen was raised in 70% and CYFRA 21-1 in 69%. Conclusions : In patients with an elevated pretreatment SCC antigen, SCC antigen normalized more frequently with combined treatment and those patients had a better DFS. Elevated SCC antigen or CYFRA 21-1 levels after treatment completion indicated residual tumor in respectively 92% and 70%. The presence of elevated posttreatment levels of SCC antigen or CYFRA 21-1 indicates the need for additional salvage surgery. SCC antigen proved to be superior to CYFRA 21-1 in predicting DFS and disease recurrence.

Clinical value of routine serum squamous cell carcinoma antigen in follow-up of patients with early-stage cervical cancer.

To investigate the contribution to recurrence detection and survival of serum squamous cell carcinoma antigen (SCC-ag) analysis in the follow-up of early-stage cervical cancer patients. Follow-up data were evaluated in patients with early-stage squamous cell cervical cancer treated by radical hysterectomy and pelvic lymphadenectomy with or without radiotherapy. Routine serum SCC-ag determination was performed at each follow-up visit. Recurrent disease occurred in 35 (16%) of 225 patients and was preceded or accompanied by serum SCC-ag elevation 26 times (sensitivity, 74%). In five (14%) of these 35 patients, elevated serum SCC-ag was the first measured clinical indicator. Desite salvage therapy, all five patients died of disease. In the other 31 patients (21 with serum SCC-ag elevation), either symptoms and/or positive signs led to recurrence detection. Median survival time after recurrence was worse (9 months; range, 2 to 112+) for patients with an elevated serum SCC-ag value at recurrence in comparison with patients with normal serum SCC-ag values (20 months; range, 4 to 96; P <.01). In 23 of the 190 patients without recurrences, serum SCC-ag values became falsely elevated. In 16 of these 23 patients, the repeat sample after 6 weeks showed a normal SCC-ag, and in seven patients benign (especially skin) disorders were found. Serum SCC-ag analysis results in earlier recurrence detection in a small proportion (14%) of patients but did not contribute to better survival. As long as treatment possibilities for recurrent cervical cancer patients are not improved, serum SCC-ag analysis should not be carried out in routine follow-up.

Pretreatment serum squamous cell carcinoma antigen: a newly identified prognostic factor in early-stage cervical carcinoma.

To investigate the prognostic value of pretreatment serum squamous cell carcinoma antigen (SCC-ag) levels in patients with cervical squamous cell carcinoma in relation to well-established conventional risk factors. Sera from 653 women treated for squamous cervical cancer between 1978 and 1994 were analyzed for the presence of SCC-ag and related to clinicopathologic characteristics and patient outcome using univariate and multivariate analyses. Increased pretreatment SCC-ag levels correlated strongly with unfavorable clinicopathologic characteristics (International Federation of Gynecology and Obstetrics [FIGO] stages IB to IV [P < or = .00005]; stages IB and IIA: tumor size [P = .0236], deep stromal infiltration [P = .00009], and lymph node metastasis [P = .0001]). After multivariate analysis, elevated pretreatment serum SCC-ag levels (P = .001), lesion size (P = .043), and vascular invasion by tumor cells (P = .001) were independent predictors for the presence of lymph node metastases. In Cox regression analysis, controlling for SCC-ag, lesion size, grade, vascular invasion, depth of stromal infiltration, and lymph node status only the initial SCC-ag level had a significant independent effect on survival (P = .0152). Even in node-negative patients, the risk of recurrence was three times higher if the SCC-ag level was elevated before therapy. The determination of pretreatment serum SCC-ag level provides a new prognostic factor in early-stage disease, particularly in patients with small tumor size. In future trials to assess the value of new treatment strategies, pretreatment serum SCC-ag levels can be used to help identify patients with a poor prognosis.

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 mu g l(-1) without any sign of malignant transformation.