International trends in incidence of cervical cancer: II. Squamous-cell carcinoma

Time trends in the incidence of squamous-cell carcinomas of the cervix during the period 1973-1991 were examined using data provided by 60 population-based cancer registries from 32 defined populations in 25 countries. Three components of the incidence trend were studied: age, calendar period of diagnosis and birth cohort. Cumulative incidence rates per 1,000 person-years for 2 groups, age ranges 25-49 and 50-74 years, were calculated from the model that best described the incidence data. A significant decline in incidence was noted in the American populations (except for US Hispanic), Australia, the non-Maori women of New Zealand, northern and western Europe (except Italy and Spain, where the rates remain stable) and Asian populations (except Malay women of Singapore, who have stable rates). These trends were of similar magnitude for the whole age range studied (25-74 years). An increasing trend, mainly restricted to younger women, was found for Slovakia, Jewish women born in Israel and the United Kingdom. In Slovenia, the increasing trend was observed for all age groups. The predominant pattern shown by cancer registries in developed countries is of a reduction in the incidence of squamous cervical cancer. This could be, at least partially, attributed to the widespread practice of screening for cervical lesions. The major exception to the pattern is observed in the United Kingdom, though the increasing incidence in young women has changed to a decrease in recent years. There are only a few series covering a long period of time in developing countries, but there is little evidence for a major impact of screening.     

Sequential p53 mutation analysis of pre-invasive and invasive head and neck squamous carcinoma

Single-stranded conformation polymorphism (SSCP) and direct sequencing were performed on uninvolved mucosa, severe dysplasia and invasive carcinoma samples from 20 patients with head and neck squamous carcinoma. Seven (35%) of the non-invasive lesions and 15 (75%) of the invasive carcinomas manifested p53 mutations. Although the majority of mutations were mis-sense, resulting in single amino acid substitution, a silent mutation encoding for the same amino acid and 2 non-sense mutations encoding a stop codon were also observed. Mutations in invasive carcinoma were mostly in exon 8 and involved codons 296, 288 and 298; non-invasive lesions showed more mutations at exons 5 to 7. Five lesions showed simultaneous mutations in 2 different exons; in 3 both non-invasive and invasive carcinomas showed primary mutation at exons 5 to 7, and invasive carcinoma showed a secondary mutation at exon 8. Different codon mutations in the same exon between dysplastic and the corresponding carcinoma samples were found in 2 cases. p53 alterations were not observed in any of the normal mucosa samples. No apparent association between p53 mutations and conventional clinicopathologic parameters, including DNA content, was found in this cohort. Our study indicates that (i) p53 alteration is an early event in the genesis of a subset of head and neck squamous carcinomas, (ii) normal mucosa within the resected specimens lacked p53 mutation, (iii) sequential mutations of different exons of the p53 gene suggests accumulation of genetic alterations during the neoplastic transformation of these lesions and (iv) the difference in codon mutation of the same exon between dysplastic and corresponding carcinoma suggests an independent clonal development. © 1995 Wiley-Liss, Inc.     

凋亡相关蛋白3（APR3）在宫颈鳞癌组织中的表达及临床意义

目的：探讨 APR3在不同宫颈组织的表达情况和临床病理意义。方法：免疫组化法（SP 法）对放化疗前后的宫颈鳞癌组织80例,CIN 90例以及正常宫颈组织30例的 APR3表达情况进行检测。结果：APR3在宫颈鳞癌中阳性表达率为81．25％,明显高于 CIN 组的31．11％以及对照组的10．00％（P ＜0．01）。放化疗后宫颈鳞癌组织中 APR3的表达率为51．25％,低于放化疗前81．25％（P ＜0．01）。APR3阳性表达率随临床分期的增高而增加（P ＜0．05）,病理分化程度的降低而增加（P ＜0．05）,有淋巴结转移者阳性表达率明显高于无转移者（P ＜0．05）。结论：APR3与子宫颈病变良恶性有关,与子宫颈鳞癌发生发展相关。放化疗可能影响宫颈鳞癌组织中 APR3的表达水平。     

CIK细胞回输降低肝癌微创介入术后复发中AFP定量检测的临床意义

Background and Objective:In patients with hepatocellular carcinoma(HCC) receiving potentially curative minimally invasive therapy,autologous cytokine-induced killer(CIK) cells were used to reduce recurrence.In this study we observed the changes in serum alpha-fetoprotein(AFP) after the treatment with CIK cells to explore if AFP could serve as a marker for predicting immunotherapeutic clinical outcome.Methods:A total of 122 patients with HCC and elevated AFP(> 25 ng/mL) received a curative treatment of trans...     

Familial invasive breast cancers: worse outcome related to BRCA1 mutations.

PURPOSE: Although all studies confirm that BRCA1 tumors are highly proliferative and poorly differentiated, their outcomes remain controversial. We propose to examine, through a cohort study, the pathologic characteristics, overall survival, local recurrence, and metastasis-free intervals of 40 patients with BRCA1 breast cancer. PATIENTS AND METHODS: A cohort of 183 patients with invasive breast cancer, treated at the Institut Curie and presenting with a familial history of breast and/or ovarian cancer, were tested for BRCA1 germ-line mutation. Tumor characteristics and clinical events were extracted from our prospectively registered database. RESULTS: Forty BRCA1 mutations were found among the 183 patients (22%). Median follow-up was 58 months. BRCA1 tumors were larger in size (P =.03), had a higher rate of grade 3 histoprognostic factors (P =.002), and had a higher frequency of negative estrogen (P =.003) and progesterone receptors (P =.002) compared with non-BRCA1 tumors. Overall survival was poorer for carriers than for noncarriers (5-year rate, 80% v 91%, P =.002). Because a long time interval between cancer diagnosis and genetic counseling artificially increases survival time due to unrecorded deaths, the analysis was limited to the 110 patients whose diagnosis-to-counseling interval was less than 36 months (19 BRCA1 patients and 91 non-BRCA1 patients). The differences between the BRCA1 and non-BRCA1 groups regarding overall survival and metastasis-free interval were dramatically increased (49% v 85% and 18% v 84%, respectively). Multivariate analysis showed that BRCA1 mutation was an independent prognostic factor. CONCLUSION: Our results strongly support that among patients with familial breast cancer, those who have a BRCA1 mutation have a worse outcome than those who do not.     

Expression of tissue inhibitor of matrix metalloproteinases (TIMP)-3 protein in invasive breast carcinoma: Relation to tumor phenotype and clinical outcome

Introduction  

Our aim was to study the expression pattern of tissue inhibitor of metalloproteinases (TIMP)-3 protein in invasive breast carcinoma, and its clinicopathological and prognostic value as well as its relation to markers indicative of the tumor phenotype.     

Epidemiology of pre-invasive and invasive malignant melanoma in Western Australia

The annual incidence rates of melanoma in Western Australia in 1975 and 1976 were estimated, by reference to hospital and pathology records. They were 4.4/ 100,000 in males and 6.2/100,000 in females for pre-invasive lesions and 18.6/100,000 and 18.8/100,000 for invasive lesions. Rates specific to particular body sites showed two distinct patterns of change with age - a progressive rise beginning about age 40 years (shown by Hutchinson's melanotic freckle and invasive melanoma of the head and neck) and an early rise beginning about age 20 years with a peak in middle-life and subsequent stabilization or decline (shown by superficial spreading melanoma, non-invasive and invasive melanoma of the lower limbs and, less typically, trunk and upper limbs). Incidence rates were highest in native-born Australians and higher in immigrants of British origin than in other immigrants. The rates in British immigrants were more than double those in the British Isles. The incidence was highest in residents of high social class areas, and in in-door rather than outdoor workers. Rates were also highest in the capital city, Perth, and the south-west corner of the State, rather than in the north where exposure of the population to ultra-violet light might be expected to be highest. In most of these respects the patterns for pre-invasive and invasive lesions were similar. Aspects of these data are inconsistent with the solar hypothesis of melanoma aetiology. It is suggested, however, that some of these inconsistencies may be explained if intermittent, intense exposure to the sun were more relevant to the aetiology of melanoma than continuous exposure.     

肝癌相关抗原calponin2的血清免疫反应及其意义

目的：检测肿瘤相关抗原calponin2对肝细胞癌(hepatocellular carcinoma, HCC)的特异性。方法：应用SEREX （serological identification of antigens by recombinant expression loning)技术检测calponin2抗原在肝癌、肺癌、胃癌、直肠癌、肝炎、肝硬化患者（各31例）及正常健康者（32人）血清的抗体阳性率。结果：相应抗体主要见于HCC患者血清,其血清阳性反应率为54.8% ;肝炎、肝硬化患者血清阳性反应率均为3.2%;肺癌、直肠癌、胃癌患者的血清阳性反应率分别是3.2%、97%和6.5%;正常人血清阳性反应率为3.1%。Calponin2抗体在肝癌血清中的阳性率最高（P<001）。Calponin2阳性率与AFP阳性率及含量、癌组织病理分级、患者年龄及γ谷氨酰转肽酶（γGT）水平无相关性。使用calponin2诊断肝癌的灵敏度、特异性和准确度分别为54.8%、95.2%和89.4%。结论: Calponin2在HCC中有一定的特异性,具有作为新的HCC血清学诊断潜在标志物的意义。     

Maternal and fetal outcome after invasive cervical cancer in pregnancy

Invasive carcinoma of the cervix is the most common gynecologic malignancy to occur during the reproductive years. To analyze the effects of pregnancy on the course and survival of invasive cervical cancer, we compared 40 women with invasive cervical cancer to 89 nonpregnant controls matched for age, calendric year of diagnosis, stage, and tumor type. Additionally, we compared the distribution of invasive cervical cancer stages among the 40 pregnant women with that among the 1,963 cases of invasive cervical cancer treated during the same 30 years in women less than 45 years of age registered in the same hospital. To evaluate pregnancy outcome, we compared babies born to women with invasive cervical cancer to babies born of women matched for maternal age and not exposed to known teratogens or reproductive risks during pregnancy. Thirty-year survival of pregnant women with invasive cervical cancer was identical to that of their matched controls. Women having invasive cervical cancer were 3.1 times more likely to be diagnosed with stage I disease (95% confidence interval, 1.6 to 6.2). Additionally, they had a significantly lower chance of being diagnosed with stages III and IV (P = .02). Babies born to women with invasive cervical cancer were similar in gestational age and rates of prematurity but had a lower birth weight than the matched controls. There were two stillbirths among the 24 pregnancies that continued to term (8%), not statistically different from the 1.1% rate for Ontario. Our data suggest that pregnancy per se does not adversely affect the survival of women with invasive cervical cancer. However, this study provides evidence that pregnant women are more likely to present with early disease because of regular, pregnancy-related obstetric exams. Moreover, there is an increased risk for stillbirth, which should lead to follow-up of these patients by a high-risk perinatal unit.     

Radioimmunoluminography: a tool for relating tissue antigen concentration to clinical outcome.

Proteins control cell function and measurement of their concentration is crucial for understanding their roles in health and disease. However, current methods for their detection in tissue sections are not quantitative. Radioimmunoluminography (RILG) is a system for direct measurement of quantity and distribution of protein in histological sections. Histological carcinomas were reacted with antigen-saturating concentrations of 125I-antibody to carcinoembryonic antigen (CEA). Antibody distribution and concentration was mapped by phosphor imaging. Radioactivity in each pixel of the digital image was proportional to antigen concentration, calculated from a standard line generated from a nitrocellulose CEA dot-blot assay. RILG gave a linear correlation with standards of known CEA concentration (r = 0.999). Six tumour xenografts with differing CEA concentrations by radioimmunoassay (RIA) were studied by RILG and immunohistochemistry (IHC). RILG gave a linear correlation with CEA by RIA (r = 0.994) but IHC failed to do so (r = 0.42). CEA levels measured by RILG, in cryostat (n = 15) and paraffin (n = 19) sections from colorectal cancer patients showed a range of CEA concentration (38.9-594 ng g(-1) and 22.5-212.5 ng g(-1) respectively). Tumour CEA concentration by RILG was significantly correlated with dose of antibody (% injected radioactivity kg(-1)) localized in tumour (P = 0.04 and P < 0.02 respectively), in patients receiving radioimmunoguided surgery. Clinical relevance of RILG is illustrated by identifying patients with high tumour CEA, most likely to benefit from antibody targeted therapy. Knowledge of the pathophysiology of many diseases may be enhanced by quantitative estimation of antigen concentration related to tissue morphology.     

Present status of treatment for invasive cervical carcinoma

The results are presented of a retrospective clinical study carried out on 341 patients affected with cancer of the uterine cervix, with lymphography in the pretreatment diagnostic work-up, treated in our Institute from January 1961 to December 1976. The clinical classification of the patients studied was: 157 cases in Stage I (46.0%), 95 cases in Stage II (27.9%), and 89 cases in Stages III and IV (26.1%). During the period considered, the therapeutic approach for carcinoma of the cervix was practically constant and in line with the therapeutic policy most frequently followed for these neoplasms. For the early stages (9/341 patients or 27.6%) preference was given to a radical surgery and postoperative radiotherapy combination; for borderline cases and "bulky" and "barrel-shaped" lesions, radiotherapy usually preceded surgical treatment to enlarge its indications and improve its results (36/341 patients or 10.5%). The cases that were more developed locally or that presented contraindications to surgery received radiological treatment alone (211/341 patients or 61.9%). Radiotherapy treatment consisted of radium therapy performed with a single application of 226Ra conventional sources, followed by percutaneous irradiation with 60Co-teletherapy in the more developed cases and/or in the presence of lymph node metastases. All the patients were submitted to diagnostic lymphography at the onset of the treatment and 92 (26.9%) had lymph node metastases. In the framework of this clinical review, the 5-year disease-free survival from onset of the treatment varied from 88.2% for the cases at Stage Ib occult, 72.5% for the cases at Stage Ib, 63.8% for the Stage II cases, to 40.5% for the cases at Stage III and IV. The presence of a pathologic report at lymphography makes a considerable difference in terms of disease-free, long-term survival after treatment     

Radioimmunoassay for tumor antigen of human cervical squamous cell carcinoma.

A heterologous antiserum for human cervical squamous cell carcinoma was prepared and specificity determined by Ouchterlony immunodiffusion and immunofluorescence studies. With this antiserum, a tumor antigen was purified from human cervical squamous cell carcinoma tissue. The specificities of the antigen and the antiserum were then re-examined by a radioimmunoassay method using 125 I-labeled purified antigen. Although normal cervical tissue extract showed a moderate cross-reactivity in the radioimmunoassay, the circulating antigen activity could not be detected in normal women or in several patients with carcinomas, whereas 27 of 35 patients with cervical squamous cell carcinoma showed detectable serum antigen activity. All aptients with advanced stages of cervical squamous cell carcinoma showed detectable antigen levels. These results indicate that there is a quantitative abnormality, at least, of this tumor antigen in patients with cervical squamous cell carcinoma and that the radioimmunoassay for the antigen is a potentially useful tool in clinical care.     

Favorable clinical outcome of cervical cancers infected with human papilloma virus type 58 and related types

To determine whether the status of human-papillomavirus (HPV) infection affects the clinical outcome of cervical carcinoma (CC), HPV genotype was prospectively determined in 94 consecutive CC cases subsequently followed for a median duration of 37.5 months. With a consensus PCR-RFLP method of HPV genotyping, 81 (86.2%) cancers were positive for HPV DNA. They were classified, according to the phylogenic similarities, into HPV-16-related (type 16, n = 45; type 31, n = 2), HPV-58-related (type 58, n = 17; type 33, n = 3; type 52, n = 2) and HPV-18-related (type 18, n = 8; type 68, n = 1) groups, and analyzed in relation to clinical outcome. The following results were observed: (i) Type-58-related HPVs were more prevalent in the old age (older than the median age of 52) group than in the young age group (41% vs. 14.6%, p = 0.045); (ii) 63% (5/8) of patients with advanced stages (III and IV) were HPV-negative, a figure much higher than that (9.3%, 8/84) of patients with early stages (stage I and II) (p = 0.002); (iii) the occurrence of adenocarcinoma or adenosquamous carcinoma was higher in the HPV-18-related group (50%) than in the HPV-16-related (33.3%) or the HPV-58-related (16.7%) groups (p = 0.024); (iv) the status of lymph-node metastasis and tumor grade did not correlate with HPV status; (v) 5-year survival rates were 90.2%, 80% and 74% for HPV-58-, HPV-16- and HPV-18-related groups, respectively (p = 0.03, after adjustment for tumor stage); (vi) in comparison with the HPV-16-related group, the relative risk of death in the HPV-58- and the HPV-18-related groups were 0.32 [95% CI, 0.07-1.49] and 1.87 [0.36-14.9] respectively. HPV genotype appears to affect the clinical behavior and outcome of cervical cancer. HPV-58-related types are prevalent in the older population, and appear to confer a favorable prognosis. Int. J. Cancer (Pred. Oncol.) 84:553-557, 1999.     

鼻咽癌颈部淋巴结转移综合治疗的远期疗效观察

目的 观察鼻咽癌放化疗配合颈部淋巴结微波热疗的远期疗效.方法 154例初治N2～N3期鼻咽癌患者随机分为对照组(78例)和热疗组(76例).对照组用氟尿嘧啶+顺铂化疗1～2周期(21 d为1周期)后原发灶常规放疗DT 70～78 Gy分35～39次,颈淋巴结转移灶DT 68～72 Gy分34～36次.热疗组放化疗方法同对照组,颈淋巴结于放疗第1周开始配合局部热疗,每次加温45min,2次/周,共8～14次.结果 热疗组、对照组5年颈淋巴结局部控制率分别为97%和77%(X2=14.24,P<0.01),远处转移率分别为37%、44%(X2=0.73,P>0.05),无瘤生存率分别为51%、21%(X2=15.91,P<0.01),总生存率分别为59%、41%(X2=5.09,P<0.05).结论 对N2、N3期鼻咽癌放化疗配合颈淋巴结微波热疗的5年颈淋巴结局部控制率、无瘤生存率和总生存率均优于单纯放化疗组.     

鼻咽癌颈部淋巴结转移综合治疗的远期疗效观察

目的 观察鼻咽癌放化疗配合颈部淋巴结微波热疗的远期疗效.方法 154例初治N2～N3期鼻咽癌患者随机分为对照组(78例)和热疗组(76例).对照组用氟尿嘧啶+顺铂化疗1～2周期(21 d为1周期)后原发灶常规放疗DT 70～78 Gy分35～39次,颈淋巴结转移灶DT 68～72 Gy分34～36次.热疗组放化疗方法同对照组,颈淋巴结于放疗第1周开始配合局部热疗,每次加温45min,2次/周,共8～14次.结果 热疗组、对照组5年颈淋巴结局部控制率分别为97%和77%(X2=14.24,P<0.01),远处转移率分别为37%、44%(X2=0.73,P>0.05),无瘤生存率分别为51%、21%(X2=15.91,P<0.01),总生存率分别为59%、41%(X2=5.09,P<0.05).结论 对N2、N3期鼻咽癌放化疗配合颈淋巴结微波热疗的5年颈淋巴结局部控制率、无瘤生存率和总生存率均优于单纯放化疗组.     

鼻咽癌颈部淋巴结转移综合治疗的远期疗效观察

目的 观察鼻咽癌放化疗配合颈部淋巴结微波热疗的远期疗效.方法 154例初治N2～N3期鼻咽癌患者随机分为对照组(78例)和热疗组(76例).对照组用氟尿嘧啶+顺铂化疗1～2周期(21 d为1周期)后原发灶常规放疗DT 70～78 Gy分35～39次,颈淋巴结转移灶DT 68～72 Gy分34～36次.热疗组放化疗方法同对照组,颈淋巴结于放疗第1周开始配合局部热疗,每次加温45min,2次/周,共8～14次.结果 热疗组、对照组5年颈淋巴结局部控制率分别为97%和77%(X2=14.24,P<0.01),远处转移率分别为37%、44%(X2=0.73,P>0.05),无瘤生存率分别为51%、21%(X2=15.91,P<0.01),总生存率分别为59%、41%(X2=5.09,P<0.05).结论 对N2、N3期鼻咽癌放化疗配合颈淋巴结微波热疗的5年颈淋巴结局部控制率、无瘤生存率和总生存率均优于单纯放化疗组.