Progression of naive intraepithelial neoplasia genome to aggressive squamous cell carcinoma genome of uterine cervix

Although cervical intraepithelial neoplasia (CIN) is considered a neoplasia, its genomic alterations remain unknown. For this, we performed whole-exome sequencing and copy number profiling of three CINs, a microinvasive carcinoma (MIC) and four cervical squamous cell carcinomas (CSCC). Both total mutation and driver mutation numbers of the CINs were significantly fewer than those of the MIC/CSCCs (P = 0.036 and P = 0.018, respectively). Importantly, PIK3CA was altered in all MIC/CSCCs by either mutation or amplification, but not in CINs. The CINs harbored significantly lower numbers of copy number alterations (CNAs) than the MIC/CSCCs as well (P = 0.036). Pathway analysis predicted that the MIC/CSCCs were enriched with cancer-related signalings such as cell adhesion, mTOR signaling pathway and cell migration that were depleted in the CINs. The mutation-based estimation of evolutionary ages identified that CIN genomes were younger than MIC/CSCC genomes. The data indicate that CIN genomes harbor unfixed mutations in addition to human papilloma virus infection but require additional driver hits such as PIK3CA, TP53, STK11 and MAPK1 mutations for CSCC progression. Taken together, our data may explain the long latency from CIN to CSCC progression and provide useful information for molecular diagnosis of CIN and CSCC.     

Fas-mediated pathway and apoptosis in normal cervix, cervical intraepithelial neoplasia and cervical squamous cancer

The aim of this study was to examine the expression patterns of apoptosis-related antigens, such as Fas, FasL, and cFLIP, in cervical squamous cells, and investigate the role of Fas-mediated apoptosis in the pathogenesis of cervical neoplasia. Using specific antibodies for Fas, FasL, and cFLIP, we examined protein expression in 19 specimens of normal cervix, 15 mild dysplasia (CIN I), 22 moderate dysplasia (CIN II), 23 severe dysplasia (CIN III), and 34 invasive squamous cell carcinoma (SCC) by immunohistochemistry. We detected the apoptotic indices by TUNEL in the same specimens. Fas expression levels were quite similar in CIN I, CIN II and the normal cervix. Though Fas expression tended to increase in grade 2 cancer compared to grade 1 cancer and CIN III, and a slight decline was present in grade 3 compared with grade 2 cancer, these differences did not reach statistical significance. Almost all CINs did not express FasL, while FasL expression increased with the grade of the tumor. Statistically significant differences could be observed between grade 1 and grade 2 (p<0.01) and between grade 2 plus grade 3 and grade 1 (p<0.001). All cases of normal cervix and CIN, except two cases of CIN III, did not express cFLIP. cFLIP expression tended to increase with the grade of the tumor. Apoptosis was determined in all samples by TUNEL. There was a decreasing tendency of apoptotic cells from normal cervix to cancers. A negative correlation between cFLIP and apoptosis (r=-0.499 and p=0.000) was observed. Deregulated Fas/FasL system and constitutive expression of cFLIP in SCC may be an important mechanism by which SCCs escape apoptosis during the malignant transformation and progression of these tumors.     

Fhit、survivin在宫颈上皮内瘤样病变与宫颈鳞癌中的表达与临床意义

目的:探讨Fhit、Survivin在正常宫颈组织、宫颈上皮内瘤样变(CIN)和宫颈鳞癌中的表达及其临床意义.方法:应用免疫组化S-P法检测Fhit,Survivin的表达情况.结果:从正常宫颈组织-CIN-宫颈鳞癌中,Fhit失表达率和Survivin表达均递增,且有统计学差异(P<0.05).Fhit失表达与宫颈癌患者的年龄、临床分期、肿瘤大小、肿瘤病理学分级和淋巴结转移均无明显相关(P>0.05).Survivin表达与宫颈鳞癌病理分级,临床分期及淋巴结转移相关(P<0.05).宫颈鳞癌中Fhit的失表达和Survivin的表达呈正相关.结论:Fhit 失表达发生在CIN期,可为宫颈癌早期诊断方法之一.Survivin则参与了宫颈癌发生、侵袭和转移的过程.Fhit与 Survivn的表达异常可能在宫颈癌的发生中起协同作用.     

Expression of cell cycle regulator p27Kip1 is correlated with survival of patients with astrocytoma.

p27Kip1 is a cyclin-dependent kinase inhibitor that negatively regulates cell proliferation by mediating cell cycle arrest in G1. This study was undertaken to assess the prognostic value of p27Kip1 for astrocytomas. Tissue samples from 130 astrocytomas (WHO grade 1, 5 cases; grade 2, 23 cases; grade 3, 64 cases; grade 4, 38 cases), including 92 primary and 38 recurrent tumors, were examined immunohistochemically for Ki-67 and p27Kip1 expression. Patient charts were reviewed for clinical presentation, and survival was followed. The p27Kip1 labeling index (LI) ranged from 2.3 to 98.4%, with a mean value of 47.5% (+/-23.4%). The p27Kip1 LI decreased with increasing tumor grade but did not correlate with other parameters. There was no correlation between Ki-67 LI and p27Kip1 LI. For patients with primary astrocytomas, the 50% survival times of those with low p27Kip1 LI (<50%) and those with high p27Kip1 LI (> or =50%) were 17.1 and 69.6 months, respectively. For patients with high-grade tumors, the 50% survival times were 13.1 months for those with low p27Kip1 LI and 33.7 months for those with high LI. On multivariate analysis, p27Kip1 was one of the most significant prognostic factors, indicating that low p27Kip1 LI was associated with poor prognosis (primary, risk ratio = 2.5, P = 0.0023; high-grade, risk ratio = 2.2; P = 0.0139). The expression of p27Kip1 was inversely related to tumor grade and positively related to favorable outcome of patients with astrocytoma, suggesting that p27Kip1 may be a candidate for prognostic factor for this tumor.     

Fhit、survivin在宫颈上皮内瘤样病变与宫颈鳞癌中的表达与临床意义

目的：探讨Fhit、Survivin在正常宫颈组织、宫颈上皮内瘤样变（CIN）和宫颈鳞癌中的表达及其临床意义。方法：应用免疫组化S-P法检测Fhit,Survivin的表达情况。结果：从正常宫颈组织-CIN-宫颈鳞癌中,Fhit失表达率和Survivin表达均递增,且有统计学差异（P〈0.05）。Fhit失表达与宫颈癌患者的年龄、临床分期、肿瘤大小、肿瘤病理学分级和淋巴结转移均无明显相关（P〉0.05）。Survivin表达与宫颈鳞癌病理分级,临床分期及淋巴结转移相关（P〈0.05）。宫颈鳞癌中Fhit的失表达和Survivin的表达呈正相关。结论：Fhit失表达发生在CIN期,可为宫颈癌早期诊断方法之一。Survivin则参与了宫颈癌发生、侵袭和转移的过程。Fhit与Survivn的表达异常可能在宫颈癌的发生中起协同作用。     

Prognostic role of p27(Kip1) expression in oral squamous cell carcinoma in Taiwan

The cyclin-dependent kinase inhibitor p27(Kip1) can inhibit the G1 to S transition of the cell cycle and is a putative tumor suppressor. Decreased expression of p27(Kip1) protein has been correlated with poor prognosis in a variety of human tumors. We examined the expression of p27(Kip1) in oral squamous cell carcinoma (SCC), epithelial dysplasia (ED) and normal oral mucosa (NOM) using antibodies to p27(Kip1). Positive p27(Kip1) nuclear staining was detected in all the specimems from ED and NOM, whereas positive p27(Kip1) staining was observed in 16 of the 63 (25%) cases of oral SCC. The labeling index for p27(Kip1) protein was significantly reduced from NOM through ED to oral SCCs, indicating that changes of p27(Kip1) protein expression may be an early event in oral carcinogenesis in Taiwan. The Kaplan-Meier analysis showed patients with p27(Kip1)-positive tumors had significantly higher overall survival than those with p27(Kip1)-negative tumors in a total of 63 patients (P=0.015) and 47 patients with areca quid chewing habit (P=0.026). Multivariate analysis showed decreased p27(Kip1) protein expression was an independent significant predictor of poor overall survival in the patients with oral SCCs. These results indicate that p27(Kip1) protein expression may serve as a putative new adjuvant prognostic marker for routine assessment of oral SCC patients.     

子宫颈鳞癌和CIN中HPV、EBV感染及其对抗原递呈细胞的影响

目的:探讨人乳头瘤病毒(human papillomavirus,HPV)、EB病毒(Epstein-Barr virus,EBV)在宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)和子宫颈浸润性鳞状细胞癌(cervical invasive squamous cellcarcinoma,CISCC)中感染状况,及其对抗原递呈细胞的影响。方法:选择CIN和CISCC为实验组并与正常鳞状上皮做对照,用原位杂交(In situ hybridization,ISH)技术检测HPV-DNA,用免疫组化SP法标记EBV和郎格罕斯细胞(Langerhans celles,LC)。结果:HPV-DNA从正常、CINⅠ、CINⅡ、CINⅢ到CISCC组,阳性率依次为0、60.0%、70.0%、78.0%和56.7%,组间存在显著性差异(P<0.005);并且各级CIN和CISCC组明显高于正常宫颈鳞状上皮(P<0.005~0.01);CINⅢ与CISCC之间存在显著差异(P<0.005)。EBV仅在CIN和CISCC中见到极少数弱阳性细胞。LC从正常、CINⅠ、CINⅡ、CINⅢ到CISCC组,阳性率依次为20.0%、71.4%、55.0%、76.5%和92.9%。S-100蛋白在各级别CIN及CISCC中表达均明显高于正常宫颈鳞状上皮(P<0.005);CISCC明显高于各级别CIN(P<0.005)。结论:随CIN级别升高到CISCC,HPV-DNA检出率并不增高,说明HPV感染引发宫颈癌的作用,可能是早期事件,提示妇科病理工作中,在CIN早期检测HPV更有意义。EBV在CIN及CISCC组织中几乎不存在。LC阳性率从正常宫颈上皮、CIN到CISCC,呈逐渐增高趋势。在CIN和CISCC中病毒感染和LC阳性率呈正相关,说明HPV感染可导致LC增多,实际工作中检测LC对了解HPV感染有一定的辅助意义。     

子宫颈鳞癌和CIN中HPV、EBV感染及其对抗原递呈细胞的影响

目的：探讨人乳头瘤病毒（human papillomavims，HPV）、EB病毒（Epstein—Barr virus，EBV）在宫颈上皮内瘤变（cervical intraepithelial neoplasia，CIN）和子宫颈浸润性鳞状细胞癌（cervical invasive squamous cellcar cinoma，CISCC）中感染状况，及其对抗原递呈细胞的影响。方法：选择CIN和CISCC为实验组并与正常鳞状上皮做对照，用原位杂交（Insitu hybridization，ISH）技术检测HPV—DNA，用免疫组化sP法标记EBV和郎格罕斯细胞（Langerhans celles，LC）。结果：HPV—DNA从正常、CINⅠ、CINⅡ、CINⅢ到CISCC组，阳性率依次为0、60．0％、70．0％、78．0％和56．7％，组间存在显著性差异（P〈0．005）；并且各级CIN和CISCC组明显高于正常宫颈鳞状上皮（P〈0．005—0．01）；CINⅢ与CISCC之间存在显著差异（P〈0．005）。EBV仅在CIN和CISCC中见到极少数弱阳性细胞。Lc从正常、CINⅠ、CINⅡ、CINⅢ到CISCC组，阳性率依次为加．0％、71．4％、55．0％、76．5％和92．9％。S-1（13蛋白在各级别CIN及CISCC中表达均明显高于正常宫颈鳞状上皮（P〈0．005）；CISCC明显高于各级别CIN（P〈0．005）。结论：随CIN级别升高到CISCC，HPV—DNA检出率并不增高，说明HPV感染引发宫颈癌的作用，可能是早期事件，提示妇科病理工作中，在CIN早期检测HPV更有意义。EBV在CIN及CISCC组织中几乎不存在。Lc阳性率从正常宫颈上皮、CIN到CISCC，呈逐渐增高趋势。在CIN和CISCC中病毒感染和Lc阳性率呈正相关，说明HPV感染可导致LC增多，实际工作中检测LC对了解HPV感染有一定的辅助意义。     

p27Kip1、PLK1在食管鳞癌中表达的临床意义

目的:探讨p27Kip1(p27)、polo-like kinase1(PLK1)在食管鳞癌(ESCC)与其癌旁组织中的差异表达及其相关性,分析其基因表达差异与ESCC的临床病理特点及蛋白表达与预后的关系。方法:RT-PCR和免疫组化检测70对ESCC与其癌旁组织中p27、PLK1的mRNA和蛋白表达情况。结果:比较70对ESCC与其癌旁组织中p27及PLK1的相对表达,p27在46例(66%)癌组织中相对表达下降,24例(34%)癌组织中相对表达增高,比较有统计学差异(P＜0.01);而PLK1在63例(90%)癌组织中相对表达增高,7例(10%)癌组织中相对表达下降,比较有统计学差异(P＜0.01);且癌组织中PLK1及p27相对低表达与患者的病理进展、淋巴结的转移和临床分期相一致(P＜0.05);癌组织中PLK1伴p27胞浆表达阳性的患者与癌组织中PLK1伴p27胞核表达阳性的患者比较,术后生存期明显缩短(P＜0.01)。结论:p27与PLK1在ESCC组织中的差异性表达与患者的临床病理特点密切相关,癌组织中PLK1伴胞浆p27表达阳性的患者预后更差。     

Protein expression of cell cycle regulator, p27Kip1, correlates with histopathological grade of non-Hodgkin's lymphoma.

The protein p27Kip1 is one of the cyclin-dependent kinase inhibitors that are known to play important roles in the regulation of cell-cycle progression. Low levels of p27 expression in malignant cells are associated with poor prognosis in patients with breast, lung, colorectal and gastric cancers. To determine the relation of cyclin-dependent kinase inhibitors to histopathological grades of B-cell non-Hodgkin's lymphomas, the expression of p27, cyclin D1 and cyclin E in lymph node tissues was investigated in 56 patients with B-cell non-Hodgkin's lymphomas by western blotting and immunohistochemical techniques. High levels of p27 expression were observed in most lymph node tissue samples (93%) obtained from patients with low grade B-cell non-Hodgkin's lymphomas, while expression was low in lymph node tissue taken from all patients with intermediate and high grade B-cell non-Hodgkin's lymphomas. The difference in p27 expression in lymphoma tissues was significant among the different histopathological grades of B-cell non-Hodgkin's lymphomas (P<0.01). The analysis of the survival time of patients showed that the reduction of p27 expression correlated with poor prognosis. Cyclin D1, showed a high level of expression in mantle cell lymphomas and high grade B-cell non-Hodgkin's lymphomas. Cyclin E showed limited expression in 18 of 31 lymphoma tissues. Both cyclin D1 and E protein expression were not significantly different among the grades of B-cell non-Hodgkin's lymphomas. These results demonstrate that the level of p27 expression in lymphoma tissue is an important parameter in the classification of B-cell non-Hodgkin's lymphomas and in the prediction of prognosis.     

Low p27Kip1 expression is associated with poor prognosis in oral squamous cell carcinoma

BACKGROUND: p27Kip1 is a cyclin-dependent kinase inhibitor which regulates the progression of cells from the G1-into the S-phase in a cell cycle. Loss of p27Kip1 is associated with disease progression and an unfavorable outcome in several malignancies. The purpose of this study was to determine whether p27Kip1 expression can be a useful prognostic factor in oral squamous cell carcinoma (SCC) patients. PATIENTS AND METHODS: p27Kip1 expression was investigated by immunohistochemistry in tissue samples from 81 patients with oral SCC. The associations between p27Kip1 expression and clinicopathological characteristics and patient survival were also analyzed. RESULTS: Significant associations were found between p27Kip1 expression and histological grade (p = 0.010), therapeutic effect (p = 0.004) and patient outcome (p = 0.005). The 5-year survival rates of p27Kip1 high- and low-expression tumours were 80.4% and 56.7%, respectively, this difference being significant (p = 0.009) by log-rank test. Multivariate analysis revealed that reduced term survival was related to low levels of p27Kip1 expression (p = 0.008) and advanced stage (stages III and IV) (p = 0.003). CONCLUSION: These results suggest that reduction of p27Kip1 plays an important role in the progression of oral SCC and is considered to be a useful prognostic factor in oral SCC patients.     

宫颈癌及其癌前病变组织中p16INK4a和PCNA的表达及临床意义

目的：探讨p16^INK4a、增殖细胞核抗原（proliferating cell nuclear antigen,PCNA）在宫颈癌及其癌前病变组织中的表达及临床意义。方法：采用免疫组化SP法检测p16^INK4a和PCNA在40例宫颈癌、33例宫颈上皮内瘤样变（cervical intraepithelial neoplasia,CIN）Ⅱ-Ⅲ、28例CINⅠ和10例正常宫颈组织标本中的表达。结果：1）p16^INK4a在正常宫颈组织中无表达。宫颈癌或CINⅡ-Ⅲ的p16^INK4a表达阳性率显著高于CINⅠ,P〈0.01。CINⅠ、CINⅡ-Ⅲ和宫颈癌PCNA表达阳性率显著高于正常宫颈,P〈0.01。p16^INK4a、PCNA表达强度随着宫颈病变程度的加重而增高,P〈0.001。2）宫颈癌不同组织学类型、病理组织分级和临床分期p16^INK4a表达阳性率及表达强度差异均无统计学意义,P〉0.05。在不同病理组织分级和临床分期中PCNA表达强度呈增强趋势,差异有统计学意义,P〈0.05。3）p16^INK4a、PCNA在CINⅠ和CINⅡ-Ⅲ组织中的表达均呈显著正相关,P〈0.01。结论：CINⅠp16^INK4a阳性表达是其发生质变的信号,PCNA可作为宫颈细胞异常增殖的灵敏标志。联合检测宫颈病变组织中p16^INK4a和PCNA的表达有助于对宫颈癌前病变进行早期诊断。     

p53和Cyclin D1在宫颈上皮肉瘤样变和宫颈鳞癌中的过表达及意义

目的　探讨CyclinD1和 p5 3在宫颈癌中过表达的意义。 方法　采用免疫组化SP法对 5 0例宫颈浸润性鳞癌、10例宫颈上皮肉瘤样变 (CIN)和 10例正常宫颈鳞状上皮中CyclinD1和p5 3蛋白进行了检测。 结果　CyclinD1和p5 3蛋白在宫颈浸润性鳞癌中过表达率分别为 70 %和 5 0 % ,CyclinD1和 p5 3在CIN中的过表达率分别为 30 %、2 0 % ,而在对照组中未出现过表达。CyclinD1在宫颈浸润性鳞癌病理Ⅱ级和Ⅲ级中的过表达率明显高于病理Ⅰ级 (P <0 .0 5 )。CyclinD1在宫颈浸润性鳞癌临床Ⅲ期中的过表达率明显高于临床Ⅱ期 (P <0 .0 5 )。p5 3在宫颈浸润性鳞癌病理Ⅱ级和Ⅲ级中的过表达率明显高于病理Ⅰ级 (P <0 .0 5 )。结论　CyclinD1和 p5 3均与细胞周期G1/S期转换有关 ,它们的过度表达可能在不同的通路以不同的机制与宫颈癌的发生和发展有关。     

Expression of FasL in squamous cell carcinomas of the cervix and cervical intraepithelial neoplasia and its role in tumor escape mechanism

BACKGROUND: To date, several mechanisms have been described by which malignant cells escape from the immune system. One of these is through the expression of FasL. The authors hypothesized that the Fas/FasL interaction enables cervical carcinoma cells to induce apoptosis of the cells of the immune system and thereby escape from them. METHODS: The authors tested the expression of FASL on the surface of cervical carcinoma tissues. Next, they stained the same cervical tissues with anti-human leukocyte common antigen and TUNEL to identify apoptotic cells. An in vitro functional assay was then done to test if the FASL expressed on the surface of cervical carcinoma cell lines was or was not responsible for inducing apoptosis in T-cells. Finally, they compared the expression of FASL on normal and dysplastic cervical tissues. RESULTS: Ninety-four percent of the cervical carcinoma tissues the authors tested expressed FasL and the majority of the apoptotic cells in the specimens were leukocytes with very few tumor cells. In the in vitro functional assay, only the Fasl expressing cell line and not the Fasl negative cell line was able to induce apoptosis of the Fas-expressing Jurkat cells. On examining the normal cervical tissues, the authors found that the expression of Fasl was confined to the basal cell layer with loss of expression observed in the suprabasal layers, which made it an immune privileged site. Conversely, there was persistent expression of FasL in the dysplastic layers in cervical dysplasia and squamous cell carcinoma specimens. CONCLUSIONS: The findings of the current study support the authors' hypothesis that persistent expression of FasL plays a role in the ability of cervical carcinoma cells to escape from the immune system.     

Immunohistochemical analysis of p53 in vulval intraepithelial neoplasia and vulval squamous cell carcinoma

Human papillomavirus (HPV) is thought to cause some vulval squamous cell carcinomas (VSCC) by degrading p53 product. Evidence on whether HPV-negative VSCC results from p53 mutation is conflicting. We performed immunohistochemistry for p53 product on 52 cases of lone vulval intraepithelial neoplasia (VIN), 21 cases of VIN with concurrent VSCC and 67 cases of VSCC. We had previously performed HPV detection and loss of heterozygosity (LOH) analyses on these samples. Abnormal p53 immunoreactivity (p53-positive) rates in HPV-positive VSCC and HPV-negative VSCC were 22% (12/54) and 31% (4/13), respectively (P<0.74). p53 immunoreactivity was associated with LOH at the p53 locus (P<0.004), but neither technique differentiated between HPV-positive and HPV-negative VSCC. p53 immunoreactivity was associated with overall LOH rates (p53-positive VSCC vs p53-negative VSCC mean fractional regional allelic loss 0.41 vs 0.24, respectively, P<0.027). LOH at 3p25 was more frequent in p53-positive VSCC cf p53-negative VSCC (70 vs 21%, respectively, P<0.007). There was a trend in p53 disruption associated with invasive disease; HPV-positive VSCC demonstrated more disruption than VIN associated with VSCC, which had more disruption than lone VIN III (22 vs 10 vs 0%, respectively, P<0.005). In all, three out of 73 cases of VIN were p53-positive. All three were associated with concurrent or previous VSCC. Meta-analysis of previous studies revealed significantly more p53 disruption in HPV-negative VSCC cf HPV-positive VSCC (58 vs 33%, respectively; P<0.0001). p53 immunoreactivity/mutation in VIN only appeared in association with VSCC. These data suggest that HPV-independent vulval carcinogenesis does not exclusively require disruption of p53, p53 disruption may work synergistically with LOH at specific loci and p53-positive VIN should be checked carefully for the presence of occult invasion.     

High frequency of loss of heterozygosity in vulval intraepithelial neoplasia (VIN) is associated with invasive vulval squamous cell carcinoma (VSCC).

Vulval intraepithelial neoplasia (VIN) is thought to be the premalignant phase of human papillomavirus (HPV)-associated vulval squamous cell carcinoma (VSCC). Various molecular events have been suggested as markers for progression from VIN to VSCC, but loss of heterozygosity (LOH) in vulval neoplasia has rarely been studied in this context. We performed LOH analysis by polymerase chain reaction (PCR) amplification of polymorphic microsatellite markers at 6 chromosomal loci (17p13-p53, 9p21-p16, 3p25, 4q21, 5p14 and 11p15). The presence of HPV was assessed using consensus PCR primers and DNA sequencing. To examine any association between LOH and the presence of invasive disease, we analyzed 43 cases of lone VIN III, 42 cases of lone VSCC and 21 cases of VIN with concurrent VSCC. HPV DNA was detected in 95% of lone VIN III samples and 71% of lone VSCC samples. Fractional regional allelic loss (FRL) in VIN associated with VSCC was higher than in lone VIN (mean FRL 0.43 vs. 0.21, p < 0.005). LOH at 3p25 occurred significantly more frequently in HPV-negative VSCC than in HPV-positive VSCC (58% vs. 22%, p < 0.04). These data suggest that genetic instability in VIN, reflected by LOH, may increase the risk of invasion. In addition, molecular events differ in HPV-positive and -negative VSCC and 3p25 may be the site of a tumor suppressor gene involved in HPV-independent vulval carcinogenesis.     

Detection of squamous cell carcinoma antigen in normal squamous epithelia and in squamous cell carcinomas of the uterine cervix

Squamous cell carcinoma (SCC) antigen is a subfraction of tumor antigen TA-4 isolated from a cervical squamous cell carcinoma. The specificity of SCC antigen and the factors influencing its release into serum were evaluated. Antigen concentrations were measured in 157 tissue extracts and in 188 sera of patients with nonmalignant or malignant gynecologic diseases. A commercial radioimmunoassay based on polyclonal antibodies (Abbott Laboratories, North Chicago) was used. Cytosol concentrations were significantly higher (P less than 0.005) in normal squamous epithelia (means = 6040 ng/mg cell protein [CP]) and in squamous cell carcinomas (means = 2483 ng/mg CP) of the exocervix than those in normal columnar epithelia and in adenocarcinomas of the endocervix, endometrium, ovary, and breast (means = 1-508 ng/mg CP). Despite the high antigen concentrations in normal squamous epithelia, elevated serum levels (greater than 2.5 ng/ml) were almost exclusively found in patients with cervical squamous cell carcinomas. The sensitivity of SCC antigen as a marker for primary carcinomas was 61%, increasing from 29% in Stage I to 89% in Stage IV. The positivity rate was higher in women with well-differentiated (78%) and moderately differentiated carcinomas (67%) than in those with poorly differentiated tumors (38%). The results show that SCC antigen is not tumor specific. The release into serum is independent of local tissue content, but is apparently influenced by the infiltrative growth, the mass, and the degree of histologic differentiation of the tumor.