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1.
We analysed 32 primary, 8 recurrent and 16 metastatic squamous cell carcinomas of the head and neck by flow cytometry to assess tumoural heterogeneity. Intratumoural heterogeneity was found in 9 of 30 primary tumours (30%). All heterogeneous tumours had diploid and aneuploid cell lines. DNA indices were different from those of the primary tumours in 3 of the 8 recurrent lesions (38%) and in 8 of the 12 metastatic lesions (67%). The results indicate that new cell lines evolve during the process of recurrence and metastasis. The incidence of recurrence, metastasis, and heterogeneity increased with the size of the tumour. Histologically, there were tumours in which the degree of differentiation and mode of invasion of primary lesions were not consistent with the results of flow cytometry in both homogeneous and heterogeneous tumours. In conclusion, multiple sampling for flow cytometric analysis is essential for better characterization of oral carcinomas.  相似文献   

2.
The aim of this study was to investigate biological heterogeneity between primary and metastatic ovarian cancer lesions from individual patients as a means of elucidating steps in clinical progression. Cancer tissue from 61 untreated patients with ovarian surface epithelial-stromal tumours was examined. p53 expression detected immunocytochemically by the PAb1801 antibody, DNA content evaluated by flow cytometry, and cell proliferation evaluated as the [3H]thymidine labelling index were investigated in primary tumours and corresponding synchronous metastases. The frequency of p53 positivity was similar in primary (62%) and metastatic (66%) sites, with an agreement between the two lesions from the same patient in 97% of the cases. Similarly, aneuploidy frequency (80%) and DNA indices were superimposable in primary and metastatic lesions from the same patient, with a 94% agreement. The frequency of aneuploidy was higher in p53-positive than in p53-negative lesions. An overall poor agreement (rs = 0.44) was observed for proliferative activity of primary and metastatic lesions, due to a heterogeneous profile in omental with respect to primary tumours, which was mainly evident in p53-positive cancers. Conversely, cell proliferation of peritoneal, abdominal and pelvic lesions was qualitatively similar to that of the primary tumour in 88% of patients.  相似文献   

3.
Mixed medullary-follicular carcinomas (MMFC) of the thyroid are rare tumours showing the morphological and immunochemical properties of both parafollicular and follicular cell lineages. Their recognition is based on a classical WHO definition, although several other patterns have been described in recent years. We investigated 11 cases of MMFC by immunohistochemistry and in situ hybridization (ISH) to analyse the structural features, the immunophenotypic profile and the calcitonin (CT) and thyroglobulin (TG) gene expression of the neoplasm. Histologically, 10 cases had mixed parafollicular and follicular cell populations in the primary tumour and 1 only in the lymph node metastasis. All cases were immunoreactive for CT (in medullary areas) and TG (in follicular areas and also in the solid component of 8/11 cases). These findings were confirmed by ISH analysis. Combined ISH and immunostaining showed that most cases had separate CT and TG gene expression, although rare cells with concurrent CT and TG gene expression were identified in 2 tumours. We conclude that (a) MMFC display heterogeneous morphological patterns and are a special type of thyroid tumour undergoing divergent differentiation; (b) in MMFC, CT and TG genes are generally not simultaneously expressed by the same cell, although dual expression of CT and TG was present in rare neoplastic elements; and (c) the origin of MMFC, whether they are derived from the ultimo-branchial body or result from neoplastic transformation of different cell populations following common oncogenic stimuli, is unclear.  相似文献   

4.
OBJECTIVES: (1) To examine the prevalence and extent of intramural metastasis in squamous cell carcinomas of the oesophagus so as to delineate the resection margins for these tumours; (2) to devise an appropriate method for measurement of these lesions which takes into account of the contraction of the specimens after resection. METHODS: Oesophagectomy specimens were prospectively collected from 96 patients (87 males, nine females) with primary oesophageal squamous cell carcinoma over a two year period. The sizes of the tumours were measured in situ, after resection and after application of muscle relaxant (to regain their in situ length). The specimens were then serially sectioned for histological examination. RESULTS: The sizes of the tumours measured after application of muscle relaxant roughly corresponded to those measured in situ. Intramural metastasis was observed in 26% of the cases. Sixty four per cent (16 cases) of these were on the oral side, 72% (18 cases) on the gastric side, and 25% (nine cases) on both sides of the tumours. The most distant extent of intramural metastasis from the primary tumour was from 0.5 cm to 7.7 cm (mean = 3.4 cm) on the oral side, and 0.5 to 9.5 cm (mean 4 cm) on the gastric aspect of the tumour. Intramural metastasis was seen only in patients in whom the primary cancer had deep muscle infiltration. Multiple neoplastic lesions could be detected in 33% of the patients. Both intramural metastasis and multiple neoplastic lesions were associated with extensive lymph node infiltration. However, they had different histological features and extent of infiltration. CONCLUSIONS: Intramural metastasis was frequently observed in oesophageal squamous cell carcinoma. This implies that excision with wide margins should be considered for local control of the disease.  相似文献   

5.
AIMS: We studied 12 cases of hyalinizing trabecular tumour of the thyroid gland (HTT) with the aim of reviewing the cytological, histological and immunophenotypic features and of investigating the relationships of HTT with other thyroid neoplasms. METHODS AND RESULTS: Eleven patients were female and one male, aged 8-74 years (median 58). Ten cases had a benign behaviour, while two cases were locally aggressive. Of the latter, one developed distant metastases and the other is a recent case. All patients are alive 6-311 months after diagnosis. Cytologically, HTT was characterized by hypercellular smears with aggregates of roundish cells having features of papillary carcinoma (nuclear grooves, vacuoles) and fragments of fibrous tissue. Histologically, prominent nesting, trabecular growth patterns and a hyaline stroma (partly positive for laminin and collagen type IV) were found. One case was associated with a papillary microcarcinoma. Two additional cases had extensive areas of papillary carcinoma. In one of these, hyalinized papillary stalks were observed. All tumours contained thyroglobulin but not calcitonin. High molecular weight cytokeratin (a marker of papillary carcinoma) was focally positive in 4/12 cases only and thyroperoxidase (a marker of follicular adenomas, but not of papillary carcinoma) was found in 3/12 cases. CONCLUSIONS: The immunophenotypic profile and the morphological features suggest that HTTs are an heterogeneous group of tumours, some of them probably representing variants of papillary carcinoma with hyalinized stroma.  相似文献   

6.
Tumour ploidy is of prognostic value in colorectal cancer, DNA aneuploid tumours having a worse outlook. Nearly all studies have concentrated on the DNA content of the primary tumour. We have examined the ploidy of the primary tumour and its lymph node metastases in 71 cases of Dukes' stage C disease, to see whether this provides greater prognostic information than the primary alone. Analysis was performed using formalin-fixed, paraffin-embedded tumour sections. Ploidy of primary and metastases was different in 20 cases (28%), aneuploid nodes being seen with diploid primaries and vice versa. Ploidy of both the primary (chi 2 = 4.86, P = 0.03) and secondary (chi 2 = 4.86, P = 0.03) tumours predicted survival in univariate analysis. Combining the ploidy of primary and nodes, three prognostic groups could be defined--diploid primaries with diploid metastases (hazard relative to both aneuploid, 0.36) had significantly better survival than cases where the ploidy of the primary and nodes were mixed (relative hazard 0.47-0.56), which did better than cases with aneuploid primary and nodes. This study demonstrates that ploidy variation between primary and secondary tumours is common, and better prognostic information may be gained by studying both.  相似文献   

7.
Isolated atelectasis of the middle lobe has been known for many years as the "middle lobe syndrome". Several clinical studies have shown that it may bae caused by malignant tumours. A 10-year study of 135 patients with isolated middle lobe atelectasis is presented. Fifty-eight patients (43%) had malignant tumours. Of 38 who had a thoracotomy, lung resection was possible in 25. In 20 patients regional or systemic dissemination of the tumour had been diagnosed before operation. Seventy-seven patients had benign diseases, of which 74 were non-specific infections. Bronchography was performed in 46 of these cases, and all had abnormal findings in the middle lobe, eight revealing definite bronchiectasis. In three cases tuberculosis was found. In 16 cases the benign diagnosis was established at thoracotomy. Only three patients out of 58 with malignant tumours lived more than five years. Atelectasis of the middle lobe is always a sign of potential malignancy especially in patients with a previously normal chest radiograph.  相似文献   

8.
In the present study the prognostic value of both DNA ploidy and the proliferative activity of tumour cells were studied in a series of 76 consecutive patients suffering from gastric tumours. DNA ploidy and the proliferative index (as measured by the percentage of S-phase cells) were determined by flow cytometry using fresh tumour specimens. The presence of DNA aneuploid clones by flow cytometry was detected in 62% of the cases (mean DNA index of 1.63 +/- 0.46; range 1.08-2.92), the mean proportion of S-phase cells being of 18.4 +/- 11.5%. In comparison with diploid cases, aneuploid tumours showed a higher proliferative activity (cases with more than 15% S-phase cells: 18.4% versus 6.1%, p = 0.0001) as well as a higher incidence of node involvement (95% versus 68%, p = 0.001). By contrast, no significant differences were detected with respect to sex, age, histologic grade and type, clinical stage, tumour size and the incidence of extranodal involvement. Upon grouping the patients according to the proportion of S-phase cells no significant differences were observed for the clinical and biological parameters explored except for an association between a high percentage of S-phase cells and the presence of DNA aneuploidy (40% versus 96%, p = 0.0001). Regarding survival the presence of DNA aneuploidy was significantly associated with poor outcome as compared to the diploid cases (median of 15 versus 26 months, p = 0.005). By contrast, the proportion of S-phase cells did not predict patients's outcome. Multivariate analysis of prognostic factors showed that the presence of DNA aneuploidy (p = 0.003) together with the histologic type (p = 0.03) and the existence of extranodal metastases (p = 0.05) were the best combination of prognostic factors for survival prediction.  相似文献   

9.
OBJECTIVE: To evaluate the balloon-occluded arterial infusion (BOAI) of cisplatin and adriamycin as a preoperative adjuvant chemotherapy in patients with bladder cancer of stage > or = T2 or in those with stage T1 and multiple large tumours. PATIENTS AND METHODS: The study comprised 120 patients with bladder cancer who underwent BOAI from November 1984 to December 1995. BOAI chemotherapy (adriamycin and cisplatin) was administered under ischaemia through a 7 F torque-control balloon catheter, both sides of which were inserted into the contralateral internal iliac artery. The regression rate of tumours and any improvement in tumour stage was assessed. RESULTS: The clinical response rate (complete or partial) was 66% and the tumour stage improved in 39% of the patients after BOAI. Of 26 patients with stage T3 a diagnosed before BOAI, 12 were diagnosed as T2 or less after treatment. Of 27 patients who underwent total cystectomy because the tumour was diagnosed as T2 after BOAI, the post-operative histopathological examination showed that 22 (82%) were stage pT1 or below. The features associated with a good response to BOAI in patients with up to pT3a disease were grade 3, non-papillary tumours with a diameter of < 3 cm. CONCLUSION: In patients diagnosed as stage T2 and T3a, or stage T1 with multiple large tumours difficult to be treat by transurethral resection, BOAI should be considered as the first choice to decrease the stage or to confirm the pathological staging.  相似文献   

10.
The results of superselective intra-arterial chemotherapy with Mitomycin C (SIAC) in cases of hepatic neoplasms continue to be poor. Survival time was related to the percentage of hepatic replacement (PHR) but only 19% of the patients with Stage I tumours (PHR < 25%) survived for over 5 years and all the others died within 4 years. The patients with hepatic metastases from colorectal cancer achieved a significantly better cumulative 5-year survival figure than those with hepatocellular cancer (P < 0.05). The median survival times for patients with hepatic metastases from colorectal cancer, hepatocellular cancer and gallbladder cancer were 15 months, 6 months and 13 months, respectively. The overall response rate was only 27% (26/97), that for primary liver cancer 20% (7/35), that for hepatic metastases from colorectal cancer 22% (8/37) and that for gallbladder cancer 44% (11/25) and the patients who responded to SIAC (n = 27) had a significantly better cumulative 5-year survival rate (P < 0.005). Cessation of SIAC was necessary in 74% (72/97) of the cases, because of tumour progression in 53% (51/97), major complications in 19% (18/97) and patient refusal in 3% (3/97). The results of this trial may be regarded as disappointing, and we are going to use SIAC for Stage I tumours only. Resection of the tumour continues to provide the only chance of a permanent cure with these patients.  相似文献   

11.
AIMS: To examine the prognostic and pathobiological importance of DNA content in oesophageal squamous cell carcinomas in Hong Kong Chinese subjects; to evaluate its association with the immunohistochemical proliferative marker MIB-1. METHODS: Paraffin wax embedded tumour tissue and adjacent normal tissue (control tissue) samples from 45 resected stage III oesophageal squamous cell carcinomas were studied using flow cytometric analysis. The DNA content and the clinicopathological data of these patients were analysed together with the MIB-1 labelling index. RESULTS: DNA aneuploidy was present in 14 (31%) of the 45 cases. However, the DNA content did not correlate significantly with the age, sex, or survival of the patients, nor the length, location, differentiation and MIB-1 labelling index of the oesophageal carcinomas. The synthetic (S) phase fraction of diploid tumours bore no relation to the patients' survival or MIB-1 score. CONCLUSIONS: Flow cytometry was not as useful as the MIB-1 labelling index in predicting the biological characteristics of the tumours and the prognosis of patients with oesophageal squamous cell carcinomas. This study does not support the routine use of DNA flow cytometric analysis in oesophageal cancers.  相似文献   

12.
OBJECTIVE: To compare single-dose and multiple instillations of epirubicin in the chemoprophylaxis of superficial bladder tumours. PATIENTS AND METHODS: In a prospective randomized and controlled study, 168 evaluable patients were assigned to three groups after transurethral resection of bladder tumour (TURBT) and histological confirmation of its superficial nature (pTa and pT1). The groups were comparable for tumour stage, grade and other tumour characteristics. In group 1, patients received a single dose of 50 mg epirubicin in 50 mL normal saline immediately after TURBT; group 2 received 50 mg epirubicin in 50 mL normal saline 1-2 weeks after TURBT and the instillations were repeated for 8 weeks and thereafter monthly to complete one year of treatment: group 3 (control group) received no adjuvant therapy after TURBT. The patients were assessed by cysto-urethroscopy, urine cytology and DNA flow cytometry 8 weeks after resection and then every 3 months during the first 2 years and 6 monthly thereafter during the next 2 years. Intravenous urography was performed annually and when otherwise indicated. RESULTS: The recurrence rate was significantly lower in the patients treated with epirubicin than in the control group (24, 25 and 52%, respectively; P < 0.001). In those receiving epirubicin, the rates of recurrence were statistically comparable (P = 0.9). Patients who had a large tumour burden showed slightly lower recurrence rates with single-dose epirubicin than with delayed maintenance therapy but the difference was statistically insignificant. Patients with a history of bladder tumours before treatment had lower recurrence rates with maintenance treatment than with a single dose (34.6 and 22.6% in groups 1 and 2, respectively); again this difference was statistically insignificant. Patients with grade 3 tumours showed a marginal difference in favour of maintenance therapy. The rates of progression amongst the three groups were 5.5, 3.4 and 9.3%, respectively, with no significant differences. The overall toxicity rates were comparable in the two treated groups (22 and 25%). CONCLUSION: With the possible exception of grade 3 tumours, single-dose immediate epirubicin is as effective as delayed maintenance therapy, with the advantage of being more cost-effective.  相似文献   

13.
A recent report has provided strong evidence for a major prostate cancer susceptibility locus (HPC1) on chromosome 1q24-25 (Smith et al, 1996). Most inherited cancer susceptibility genes function as tumour-suppressor genes (TSGs). Allelic loss or imbalance in tumour tissue is often the hallmark of a TSG. Studies of allelic loss have not previously implicated the chromosomal region 1q24-25 in prostate cancer. However, analysis of tumour DNA from cases in prostate cancer families has not been reported. In this study, we have evaluated DNA from tissue obtained from small families [3-5 affected members (n = 17)], sibling pairs (n = 15) and sporadic (n = 40) prostate tumours using the three markers from Smith et al (1996) that defined the maximum multipoint linkage lod score. Although widely spaced (12-50 cM), each marker showed evidence of allelic imbalance in only approximately 7.5% of informative tumours. There was no difference between the familial and sporadic cases. We conclude that the incidence of allelic imbalance at HPC1 is low in both sporadic tumours and small prostate cancer families. In this group of patients, HPC1 is unlikely to be acting as a TSG in the development of prostate cancer.  相似文献   

14.
Superficial leiomyosarcomas are rare tumours. The lesions confined to the dermis, contrary to those involving the subcutis, have been reported to carry a favourable prognosis. A retrospective study of 41 consecutive cases of surgically treated intradermal and subcutaneous leiomyosarcomas was undertaken in order to determine the prognostic factors that may influence the survival of these patients. Seven tumours were predominantly intradermal and 34 involved the subcutaneous tissue. Fifty-four percent of the tumours were located in the lower extremities. All cases stained positively for smooth muscle antigen and 66% for desmin. The tumours were classified with regard to tumour grade I (low grade, 3%), II (intermediate, 12%), IIIA (high grade, 46%) and IIIB (high grade, 39%). In all patients, follow-up information was available. Mean follow-up time was 5 years. The patients with intradermal tumours were all alive without signs of recurrence, whereas 14 of those with leiomyosarcomas involving the subcutis have died with pulmonary metastases. Our study confirms that "pure" intradermal leiomyosarcomas independent of tumour grade behave in a benign fashion, probably due to small tumour size. Tumour size > or = 5 cm, deep localization with fascia involvement, and high malignancy grade (IIIB) were found to deteriorate survival based on a univariate analysis. However, in a multivariate analysis only tumour size was found to be an independent prognostic factor.  相似文献   

15.
A retrospective study of DNA flow cytometry (FCM) in paraffin-embedded tissues of urinary bladder transitional cell carcinoma (TCC) was performed on 239 biopsy samples taken from 81 patients in the period from 1984 to 1994. 210 (87%) were analysable. Of these samples 21 patients had multiple biopsies taken from large tumours and/or bladder mucosa showing an endoscopically normal appearance. DNA-FCM results have been evaluated comparing ploidy and histopathological grade, clinical stage and different clinical status, i.e., first diagnosis, recurrence and patients who died from bladder cancer. Our results indicate that 'diploid' FCM correlated with a better prognosis, whilst DNA aneuploid correlated with malignancy and a poorer prognosis. There was a trend to an increasing incidence of DNA aneuploidy as the grade of the tumour rose and the proportion of biopsies with aneuploidy was significantly higher in malignant tissue samples, recurrences and in biopsies from patients who died from TCC than in other groups. In 12 patients from whom several biopsies were obtained, samples from recurrences had significantly higher DNA aneuploidy than those from the first diagnosis.  相似文献   

16.
The study was performed to assess the effect of accelerated radiotherapy on oxygenation of primary tumours and metastatic nodes in patients with advanced head and neck tumours. In 14 patients with head and neck tumour, oxygen tension (pO2) was evaluated in normal tissues and tumours (primary tumour or metastatic neck node) before (0 Gy) and after 2 weeks (32 Gy) of accelerated radiotherapy (70 Gy in 3.5 weeks, with three daily fractions). Radiotherapy was combined with carbogen breathing in 5 patients. pO2 was measured using a polarographic technique. For pooled normal tissues, median pO2 was 38 mmHg before treatment and 46 mmHg after 2 weeks. For tumours, very low values (< 2 mmHg) represented 20% of the recorded values before treatment and 10% after 2 weeks. The relative increase in tumour oxygenation was more pronounced for primary tumours (median pO2 12 mmHg before treatment versus 26 mmHg after 2 weeks, P < 0.05) than for metastatic nodes (respectively, 20 and 27 mmHg P = 0.1). For the 5 patients who breathed carbogen during accelerated radiotherapy, the median pO2 was 44 mmHg at 2 weeks, compared with 13.5 mmHg before treatment (P = 0.05). Very low pO2 values, corresponding to tumour hypoxia, were found in the tumours (primary and metastatic neck nodes) prior to accelerated treatment. During the first 2 weeks of accelerated treatment, an increase in median pO2 was found in nine of the 14 tumours, together with a decrease in the frequency of very low values.  相似文献   

17.
Abnormal cell proliferation is controlled by opposing actions of oncogene products (stimulatory) and tumour suppressor gene (TSG) products (inhibitory). The former are dominantly acting, i.e. only one copy needed for tumorigenesis, whilst for TSG both copies of the gene must be inactivated so these are recessive at a cellular level. For anterior pituitary tumours only one oncogene (Gsp) has been identified in a variable proportion (4-40%) of a single tumour subtype (somatotrophinomas). Contrariwise, allelic deletion studies, using a PCR-based microsatellite polymorphism analysis of DNA extracted from archival specimens, have shown significant loss of heterozygosity in 20-40% of all tumour subtypes at the locus of the putative MEN-1 gene (chr. 11q13); the retinoblastoma gene (chr. 13q 12-14), and 10q26. Moreover, these DNA microdeletions were concentrated in radiologically invasive tumours compared to noninvasive tumours (modified Hardy gdes 3 and 4 vs. 1 + 2). In addition, 50% of Cushing's adenomas showed presence of p53 immunopositivity, though no point mutations in exons 4-9 were found, by SSCP analysis, to account for this. These studies show that analysis of TSGs in pituitary adenomas may provide clues to their pathogenesis, and more importantly relate to clinical behaviour of the tumour, and hence aid decisions regarding management.  相似文献   

18.
OBJECTIVE: To describe the clinical course and histological features of transitional cell carcinoma (TCC) of the bladder with microcysts. PATIENTS AND METHODS: Among 940 patients with bladder TCC diagnosed at our institution during a 5 year period. 12 (1.2%; eight men and four women, mean age 71.1 years, range 52-85) were diagnosed histologically as having microcystic TCC. Sections of the tumours were stained with haematoxylin and eosin, periodic acid-Schiff and Alcian blue and clinical data obtained from the patients' records. RESULTS: Of the 12 patients with bladder TCC with microcysts, three had tumours confined to the epithelium, six had tumour invasion of the lamina propria and three had muscle invasion. One patient had low-grade TCC and 11 had high-grade TCC; six patients had a second primary tumour; three had a colon carcinoma, one a villous adenoma of the caecum, one a locally advanced carcinoma of the prostate and the last a squamous cell carcinoma of the uterine cervix. CONCLUSIONS: Microcystic TCC was associated with high-stage and high-grade bladder tumours and with other primary tumours, especially of the colon. Screening these patients for asymptomatic tumours of the colon is suggested.  相似文献   

19.
Immunohistochemical expression of the tumour associated mucin-type glycoprotein A-80 was investigated in a series of 173 breast cancer patients with a clinical follow-up between 13 and 19 years. A routine immunoperoxidase technique was used in formalin-fixed, paraffin-embedded surgical tumour specimens. One hundred and fifty of 173 tumours (87%) immunostained with MAb A-80. The degree of A-80 immunoreactivity was related to the tumour grade but not to lymph node status, tumour size, or nuclear DNA distribution pattern. In univariate analysis the degree of A-80 expression was found to be of significant prognostic value both in node negative and in node positive breast cancer patients (P = 0.03). Patients with non-A-80 immunoreactive tumours had significant longer distant metastases-free survival times and fewer relapses than women with carcinomas composed of A-80 immunoreactive tumour cells. This prognostic value was reduced in a multivariate analysis, including lymph node status, tumour size, and nuclear DNA distribution pattern, but retained borderline significance (P = 0.08). In conclusion, the findings of this study indicate that expression of the mucin-type glycoprotein A-80 as determined by immunohistochemistry seems to be related to clinical outcome in breast cancer patients.  相似文献   

20.
The DNA content of 85 ductal breast cancers of different histological grades was evaluated using static cytometry and correlated with immunocytochemical expression of p53 protein in tumour cells in cytological material. A statistically significant difference was observed between p53 protein expression and grade of malignancy (P < 0.001). The percentage of euploid tumours significantly decreased from grade I through grade II to grade III tumours (P < 0.001). Clonal DNA heterogeneity was observed in 26.6% of cases analysed and was correlated with p53 protein expression (P < 0.001). These changes probably reflect genomic alterations which may affect potential malignancy of breast cancer.  相似文献   

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