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.     

Cervical carcinoma: a comparison of four potential biochemical tumor markers

A longitudinal study of circulating immune complexes (CIC), cancer antigen 125 (CA125), carcinoembryonic antigen (CEA) and a sub-fraction of the TA-4 squamous cell carcinoma tumor-associated antigen (SCC) has been undertaken in 38 patients with cervical carcinoma. Pre- and post-treatment values have been compared with those obtained in well-defined clinical remission and relapse phases of their disease. Each tumor marker was assessed in terms of "lead time" before clinically obvious recurrent disease became evident. The data from the four subjects with adenocarcinoma of the cervix gave equivocal results and no firm conclusions could be drawn. However, for the 34 patients with squamous cell carcinoma the medium value (data was skewed) for SCC was elevated above normal in the presenting pretreatment sera (4.5 ng/ml) and significantly fell to 2.5 ng/ml post-treatment (P less than 0.01). A similar pattern was not apparent for CIC, CEA, or CA125 data. When results were examined for an individual patient, of those with recurrent squamous cell lesions who died, 12/24 demonstrated elevated, and rising SCC values before clinical evidence of the disease and a further 6 (25%) at the time recurrence was clinically evident. This information gave lead times of between 2 and 52 months (median 13 months) for 75% of patients. Only 1 subject had values which remained in the normal range (less than 2 ng/ml) even though their disease was progressive. Similarly of the subjects still in clinical remission 8/9 had values within the normal range. The data for CIC, CA125, and CEA were not individually useful as a marker. Furthermore, combining the data from all analytes to give a panel of potential markers did not improve the prognosis already evident with SCC alone. It has therefore been concluded that SCC is a useful biochemical marker of the progression of squamous cell carcinoma of the cervix.     

An immunofluorescent study of basement membranes in squamous cell carcinoma of the cervix, vagina, and vulva.

Basement membranes of 33 samples of in situ or invasive squamous cell carcinomas of the cervix uteri, vagina, and vulva were studied by defined immunofluorescence technics. Pooled serum from patients with bullous pemphigoid, containing specific antibody to squamous epithelial basement membrane, was utilized. Essentially normal basement membranes were found in all cases of in situ carcinoma and in 18 cases of invasive carcinoma. Basement membranes appeared poorly formed in three specimens with invasion and were absent in the remaining three. These findings support the premise that penetration of the basement membrane is not a valid criterion for distinguishing in situ from invasive squamous cell carcinoma.     

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%.     

The prognostic significance of carcinoembryonic antigen determinations in patients with adenocarcinoma of the cervix

Pretreatment levels of carcinoembryonic antigen (CEA) correlate well with the extent of disease in squamous cell and adenocarcinoma of the cervix. These two tumor types, however, have significantly different capacities for CEA release. The prognostic significance of pretreatment CEA determinations in squamous cell cancers is restricted to a subpopulation of these tumors and low values are equivocal. The present paper reports a long-term follow-up of 54 patients with adenocarcinoma of the cervix, all stages. It was found that no patient, regardless of stage, with an initial value over 15 micrograms/liter survived the disease. In the range between 5 and 15 micrograms/liter the recurrence rate was 67%. Patients with initial values under 5.0 micrograms/liter had an estimated 5-year survival of 90% in contrast to 11% if pretreatment values were over this limit. In Stage I, only 1 out of 8 patients with pelvic lymph node metastasis had a pretreatment value under 5.0 micrograms/liter. CEA determinations are of definite value in the planning of treatment and follow-up of patients with adenocarcinoma of the cervix.     

Clinical significance of tumor associated antigen TA-4 in gynecologic tumors

Serum levels of TA-4, a tumor associated antigen of cervical squamous cell carcinoma, were measured in various gynecologic tumors with a RIA kit (DAINABOT). Immunohistochemical localization of TA-4 was also evaluated in the squamous cell carcinoma of the cervix. Serum TA-4 levels were elevated in 8.3% of patients with CIS, in 25% with stage Ia, in 56% with stage Ib, in 83% with stage II, in 75% with stage III and IV and in 100% with recurrent squamous cell carcinoma of the cervix, respectively. No patients were positive for TA-4 in endometrial and ovarian cancers. Serum TA-4 levels declined distinctively after treatment in accordance with the disappearance of initial tumors in some patients with advanced carcinoma. TA-4 was demonstrated immunohistochemically in 2 out of 8 CIS, 3 out of 8 microinvasive carcinoma, 4 out of 4 keratinizing type, 7 out of 7 large cell type and 3 out of 6 small cell type of invasive squamous cell carcinoma, respectively. In each type of carcinoma, TA-4 was positive in the differentiated cells. Similarly, it was found in the differentiated layers of normal squamous epithelium excluding the immature cells of the basal layer.     

Squamous cell carcinoma antigen: pretreatment levels as an indicator of advanced or metastatic disease

Pretreatment values of squamous cell carcinoma antigen (SCC) were obtained in 100 consecutive patients with squamous cell carcinoma of the cervix presenting to the Regional Gynaecological Oncology Centre in Gateshead, UK. Nine patients deemed to have locally advanced disease not suitable for primary surgery had elevated levels. Ninety-one patients were suitable for primary surgery. Sixty-seven had normal SCC levels, two of which had lymph node metastases. Twenty-four had elevated SCC levels, 14 of which had lymph node metastases. Two early recurrences have been detected in the raised SCC group where no lymph node metastases were present. Elevated levels of SCC in the pretreatment assessment indicate a high risk of lymph node metastases and of developing recurrent disease after primary surgery.     

Carcinoma of the cervix, FIGO Stage IB: treatment failures

All patients with carcinoma of the cervix, FIGO Stage IB, treated at the University of Minnesota Hospitals during a 10-year period were reviewed. Of the 220 patients 31 (14.0%) developed recurrent disease and did not survive. Thirteen patients had pelvic wall recurrences, with concurrent cervical involvement. No patient had a resectable pelvic recurrence. Hysterectomy was subsequently performed on 10 of the 172 patients who received radiation therapy. Carcinoma was not present in any of the operative specimens although two patients with adenocarcinoma later died of metastatic cancer. Median time of recurrence was 9 months, with median survival following recurrence of 6 months. Cervical cytology was not of value in the early diagnosis of recurrent disease. The 5-year adjusted actuarial survival rate for patients with adenosquamous carcinoma was significantly lower than that for patients with squamous cell carcinoma. The median age of patients not surviving with adenosquamous carcinoma was significantly lower than that for patients not surviving with squamous cell carcinoma. Patients with invasive carcinoma presumably confined to the cervix may have disseminated disease. It is essential such selected patients receive primary treatment that includes systemic therapy.     

Recurrent vulvar carcinoma in the intervening tissue bridge in early invasive stage I disease treated by radical vulvectomy and bilateral groin dissection through separate incisions

Early invasive stage I squamous cell carcinoma of the vulva treated with radical vulvectomy and bilateral inguinofemoral lymphadenectomy rarely recurs, particularly when the lymph nodes contain no metastatic tumor. Primary radical surgery in this patient utilized separate groin incisions, and recurrent tumor developed in the tissue bridge between the groin scar and the vulva. Reexploration showed numerous inguinofemoral nodes to subseqently contain recurrent carcinoma. Literature regarding early, "microinvasive," squamous cell carcinoma of the vulva is reviewed.     

Some epidemiologic aspects of carcinoma of the vulva in Israel

A nationwide study of squamous cell carcinoma of the vulva in Israeli Jewish women has been conducted for a comparison of the incidence, the age pattern and the ethnic distribution of squamous cell carcinoma of the vulva to those of squamous cell carcinoma of the cervix. The mean annual incidence rates by age in squamous cell carcinoma of the vulva rise continuously to age 70+ while in squamous cell carcinoma of the cervix a plateau is reached at age 40 to age 69. In contrast to the relatively low incidence of squamous cell carcinoma of the cervix in Israeli Jewish women, the age-specific incidence rates of squamous cell carcinoma of the vulva are similar to those of white women in the United States. On the other hand, there is a trend to a higher incidence of both squamous cell carcinoma of the cervix and squamous cell carcinoma of the vulva in the North African ethnic group of Israeli Jewish women.     

Pelvic exenteration, University of Michigan: 100 patients at 5 years

One hundred patients undergoing pelvic exenteration (total 69, anterior 13, posterior 18) at the University of Michigan Medical Center from 1964-1984 are reported. All patients were followed for at least 5 years or until time of death. The overall cumulative survival was 66% at 3 years and 61% at 5 years. The age of the patients ranged from 21-74 years (median 53). The type of pelvic neoplasm included squamous cell of the cervix, 57; adenocarcinoma of the cervix, nine; squamous cell carcinoma of the vulva, 12; squamous cell carcinoma of the vagina, eight; vaginal sarcoma, four; adenocarcinoma of the vagina, one; adenocarcinoma of the endometrium, four; uterine sarcoma, four; and adenocarcinoma of the ovary, one. The cumulative 5-year survival was significantly related to the presence of metastatic disease to the regional lymph nodes (8% 3-year and 0% 5-year survival), time interval from primary diagnosis to exenteration (within 1 year 44%, 1-10 years 60%, and over 10 years 95%), and cell type (squamous cell 68%, sarcoma 62%, and adenocarcinoma 26%). Patients with squamous cell carcinoma of the cervix (N = 57) had a cumulative 5-year survival of 73%, compared with nine patients with adenocarcinoma of the cervix, who had a 22% 5-year survival. No significant difference in survival existed for the type of exenteration, original stage of squamous cell cervical carcinoma, size of recurrent squamous cell lesion, or age of the patient. Early or late complications occurred in 49 patients. Two patients died in the postoperative period. Small-bowel obstruction was the most common complication seen in this series.     

A clinical study on multiple tumor markers following therapy in patients with uterine cervical carcinoma

In order to evaluate the clinical significance of multiple tumor markers, plasma levels of carcino-embryonic antigen (CEA), squamous cell carcinoma-related antigen (SCC), tissue polypeptide antigen (TPA) and immunosuppressive acidic protein (IAP) were measured before and after treatment in 136 patients (89 surgery cases and 47 radiotherapy cases). The patients had invasive cervical carcinoma (stages I-IV). The effect of radiotherapy was examined by cytology and biopsies obtained by colposcopy. For CEA, SCC and TPA there was a significant reduction (p less than 0.01) in values between the pretreatment and posttreatment periods, but plasma IAP was transiently increased after operation. Cytology and histology revealed negative rates of 95.6% and 86.7%, respectively, after radiotherapy. Regarding recurrence, for the negative groups and positive groups plasma CEA, SCC, TPA and IAP were determined in 24 patients with stage IIIb before radiotherapy. Only the CEA concentration showed a good correlation with the outcome (p less than 0.01). Effective serial plasma determinations of CEA, SCC and TPA in patients with cervical carcinoma following therapy may often be useful in the evaluation of therapy as well as in the earlier detection of recurrent disease.     

Invasive squamous carcinoma of the vulva in young patients

Over a 30-year period, 17 patients below the age of 35 with invasive squamous carcinoma of the vulva were identified, 8 of whom (47.1%) had “microinvasive” disease. Venereal diseases and condyloma accuminata were not predisposing factors. Immunosuppression was a contributory factor in 2 patients. Although carcinoma in situ was antecedent in only 1 patient, it was an associated lesion in 87.5% of patients with “microinvasive” and 22.2% of patients with invasive carcinoma. The nature and course of this disease in young patients do not differ from the elder counterpart. Prolonged follow-up of these patients has revealed increased susceptibility of the perineum, vagina, and cervix to multiple neoplasms.     

CA-125: a potential prognostic indicator in patients with cervical cancer?

We evaluated 104 patients with newly diagnosed carcinoma of the cervix. Pre- and post-therapy and follow-up CA-125 levels were measured in 64 patients. Fifty-five patients (86%) had squamous cell carcinoma and 9 (14%) had adenocarcinoma of the cervix. At initial presentation 19 (30%) had CA-125 levels greater than 35 U/ml, 12 (19%) had levels of 16-35 U/ml, and 33 (51%) had levels less than 16 U/ml. Of the 11 patients who had pre- and post-treatment levels greater than 35 U/ml, 10 are dead of the disease and 1 is alive with persistent or recurrent disease. Of the 20 patients with elevated CA-125 levels at presentation who reverted to normal after therapy, 19 are clinically without evidence of disease at 14-46 months (median 27 months). Of the 33 patients with normal pre- and post-therapy CA-125 levels, 31 are clinically without evidence of disease. Two of these thirty-three patients had increasing CA-125 levels during routine follow-up and both have disease recurrence confirmed. There was no apparent correlation between CA-125 level and tumor type, tumor grade, or stage of disease. Our data suggest that patients with initially elevated CA-125 levels that revert to normal after therapy have a favorable prognosis. Persistent elevation of CA-125 levels during and after therapy in patients with carcinoma of the cervix was associated with a poor prognosis.     

Stage IA2 squamous carcinoma of the cervix: difficult diagnosis and therapeutic dilemma

The International Federation of Gynecology and Obstetrics instituted a change in the classification for carcinoma of the cervix with a new substage IA2. The criteria for this substage exceed the generally accepted criteria for microinvasion. Fifty patients with early invasive squamous cell carcinoma of the cervix were treated from 1976 through 1983 with a cone biopsy followed by a radical hysterectomy and pelvic lymph node dissection. These patients were reviewed to evaluate the ability to make the histologic diagnosis and to examine the natural history of the disease with maximal treatment. Histologically positive margins were found at the time of cone biopsy in 66% (33/50) of the patients. Negative margins at the time of cone biopsy were identified in 34% (17/50) of the patients. Residual invasive disease at the time of radical hysterectomy was found in 24% (4/17) of the patients with negative margins. Two of the 50 patients had positive lymph nodes. Three patients had recurrent metastatic disease. This study demonstrates that a preoperative diagnosis of stage IA2 invasive squamous cell carcinoma of the cervix is a difficult diagnosis to establish and creates a therapeutic dilemma regarding treatment.     

Vulvar invasive squamous cell carcinoma occurring in a young woman with systemic lupus erythematosus

BACKGROUND: Although several studies have demonstrated a possible relationship between systemic lupus erythematosus (SLE) and non-Hodgkin's lymphoma, Hodgkin's lymphoma, leukemia and several solid tumors, it is still debatable whether SLE patients have an increased incidence of cancer overall. CASE: We describe a 25-year-old patient with SLE who developed invasive squamous cell carcinoma of the vulva. The patient underwent radical vulvectomy and bilateral groin sentinel lymph node dissection and until to date, one year after surgery, she is alive without evidence of recurrent disease. CONCLUSIONS: Only three cases of vaginal/vulvar cancer associated with SLE have previously been mentioned in the literature, but not described in detail. This is the first detailed case report in the literature of vulvar invasive squamous cell carcinoma occurring in a SLE patient. It can only be speculated that the SLE itself and/or the treatment with immunosuppressive drugs provoked malignant transformation and the development of vulvar squamous cell carcinoma in such a young patient.     

CA-125: A potential prognostic indicator in patients with cervical cancer?

We evaluated 104 patients with newly diagnosed carcinoma of the cervix. Pre- and post-therapy and followup CA-125 levels were measured in 64 patients. Fifty-five patients (86%) had squamous cell carcinoma and 9 (14%) had adenocarcinoma of the cervix. At initial presentation 19 (30%) had CA-125 levels >35 U/ml, 12 (19%) had levels of 16–35 U/ml, and 33 (51%) had levels <16 U/ml. Of the 11 patients who had pre- and post-treatment levels >35 U/ml, 10 are dead of the disease and 1 is alive with persistent or recurrent disease. Of the 20 patients with elevated CA-125 levels at presentation who reverted to normal after therapy, 19 are clinically without evidence of disease at 14–46 months (median 27 months). Of the 33 patients with normal pre- and post-therapy CA-125 levels, 31 are clinically without evidence of disease. Two of these thirty-three patients had increasing CA-125 levels during routine follow-up and both have disease recurrence confirmed. There was no apparent correlation between CA-125 level and tumor type, tumor grade, or stage of disease. Our data suggest that patients with initially elevated CA-125 levels that revert to normal after therapy have a favorable prognosis. Persistent elevation of CA-125 levels during and after therapy in patients with carcinoma of the cervix was associated with a poor prognosis.     

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.     

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.