Tylosis oesophageal cancer mapped.
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Chromosome Mapping↗
Biomedical subjects
J K Field
Publications and source records attributed to J K Field.
The level of cervical lymph node metastases: their prognostic relevance and relationship with head and neck squamous carcinoma primary sites.
It would seem logical that patients with nodal metastases low in the neck would fare less well than patients with disease high in the neck. The penultimate UICC classification suggested that neck node level was important although there was no mention of this in the most recent classification. In addition, patients with carcinomas at the various sites would be expected to have different patterns of nodal involvement. Of 3419 patients with head and neck squamous carcinoma on the Liverpool University Head and Neck Unit database, 947 had neck node metastases. The neck node levels were coded as (I) sub-mandibular, (II) above the thyroid notch, (III) below the thyroid notch and (IV) supra-clavicular/posterior triangle nodes. Levels II and III contained the deep jugular chain. The relationship between node level and site and sub-site and survival were analysed with particular emphasis on multivariate methods. The 5-year survival for the whole group was 51% and survival fell with decreasing node level (I-IV) being 37% for sub-mandibular nodes, 32% for deep cervical nodes and 25% for lower deep cervical nodes. The 18-month survival for supra-clavicular and posterior triangle nodes was 21%. The difference in survival was significant (chi 2(3) = 24.42, P < 0.001). Multivariate analysis confirmed that as the level of the nodes fell from the sub-mandibular region to the supra-clavicular region the prognosis worsened (estimate = -0.3378, P = 0.0003). Level II (upper deep cervical) nodes were the most commonly involved with regards to all primary sites and formed 69% of all neck node metastases.(ABSTRACT TRUNCATED AT 250 WORDS)
Carcinoma, Squamous Cell↗
The treatment of early squamous cell carcinoma of the piriform fossa.
The treatment of early piriform fossa cancer can be either primary radiotherapy with salvage surgery, if necessary, or with primary surgery. The present study investigates 65 patients with T1, > or = 2 or T3 stage disease with no cervical lymph node metastases at presentation. Of this group, 17 were treated by primary irradiation, 34 underwent primary surgery and 14 were unsuitable for any curative treatment. The adjusted actuarial 5-year survival rate for those patients receiving primary radiotherapy was 55% (95% CI 16-78%) and for the surgery group it was 44% (95% CI 18-67%). This difference was not significant (chi 2(1) = 1.29). The median survival for untreated patients was 7 months (4-12 months). There was no significant differences in the time to recurrence at the primary site or in the neck, or in survival after recurrence at these sites. Thirty-five per cent of patients treated by primary irradiation were controlled at the primary site compared with 68% in the surgical group. Failure in the neck was similar for the two groups at 12% and 15% respectively. Salvage surgery was effective for the radiotherapy group with eight out of 11 patients being suitable for treatment. In the final analysis in the radiotherapy group two patients were alive and with their larynx and two alive without their larynx, the remainder of patients having died from the original tumour, intercurrent disease or second primary tumours. The survival figures for the surgery group were proportionately similar except of course, that all patients had lost their larynx.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
The detection of the c-myc and ras oncogenes in nasopharyngeal carcinoma by immunohistochemistry.
Forty-one paraffin embedded specimens of primary nasopharyngeal carcinoma (NPC) were examined to investigate the expression of c-myc and ras oncogenes. Sections were stained with the monoclonal antibodies myc 1-9E10 or ras Y13-259 and binding was detected using the ABC method. The intensity of staining for each tumour was assessed as nil, moderate or intense. The results indicated that 9 (22%) had intense staining for the c-myc oncogene, 28 (68%) had moderate staining and only 4 (10%) showed no staining. For the ras oncogene, 8 (19%) had intense staining, 22 (54%) moderate staining and 11 (27%) showed no staining. The patient's clinical data indicated no correlation between the expression of either c-myc or ras p21 and age, sex, smoking, tumour stage, antibody titre to EBV, or family history. No correlation was found between ras p21 expression and survival; however, overexpression of the c-myc oncogene correlated with a poor prognosis (p < 0.05). This study is consistent with investigations demonstrating that c-myc expression correlates with poor survival in head and neck tumours.
Adult↗
p53 expression and mutations in squamous cell carcinoma of the head and neck: expression correlates with the patients' use of tobacco and alcohol.
53 expression was assessed in 93 head and neck squamous cell carcinoma patients using CM-1, DO-7, and DO-1 antibodies. Sixty eight percent was found to have positive nuclear staining. The frequency of p53 mutations were investigated in 13 patients using single-stranded conformational polymorphism (SSCP) analysis of DNA fragments that had been amplified by the polymerase chain reaction (PCR). P53 gene mutations were analyzed by SSCP in exons 4 to 7 of 13 patients, and nine were found to have mutations in exon 4; two of these patients also had a mutation in exon 5. In the group of 93 patients, p53 overexpression was found to correlate with the patients' history of heavy smoking (p < 0.01). We also analyzed the drinking and smoking history of 71 of these patients by logistic regression analysis and found that heavy smoking correlates with p53 overexpression (p < 0.05), but heavy drinking was not found to be significant. However when both smoking and drinking histories were assessed together, a correlation was found (p < 0.05). Future work may indicate that specific p53 mutations are associated with patients who have a history of heavy drinking and smoking.
Alcohol Drinking↗
Loss of heterozygosity studies on chromosome 17 in head and neck cancer using microsatellite markers.
In this study we have analysed 38 squamous cell carcinomas (SCC) two basal cell carcinomas (BCC), a malignant salivary gland carcinoma, a neurosarcoma and a Warthins carcinoma, all isolated from patients with head and neck cancers. These tumour types have been examined by PCR for loss of heterozygosity (LOH) on both arms of chromosome 17 using nine polymorphic microsatellite markers. LOH on 17p in SCCHN was found to be 50% (19/38), and often involved TP53 (42%) but more frequently involved the CHRNB1 locus (56%). Twelve tumours showed loss of heterozygosity on 17q (34%) and ten of these also had loss on 17p. Four SCCHN tumours lost an entire copy of chromosome 17. It was of particular note that 77% (10/13) of the SCCHN at the hypopharyngeal site had LOH at CHRNB1. We propose from our data that the 17p12-p11 region contains a novel predisposing gene for hypopharyngeal SCCHN that may function as a tumour suppressor gene.
Basal Cell Carcinoma↗
Exposure to cigarette smoke and expression of the protein encoded by the p53 gene in bronchial carcinoma.
Mutation of the onco-suppressor gene encoding the protein known as p53 may cause synthesis of a mutant p53 protein which can bind to and inactivate its wild-type equivalent. This protein is detectable in many malignant neoplasms, including bronchial carcinoma, and has been associated with cigarette smoking. Of 59 tissue biopsy specimens of primary bronchial malignancies immunolabeled for p53 by the avidin-biotin technique using the antibodies PAb 1801, CM1, and D07, 13 (22%) expressed the protein. Of these 13 patients, 10 (77%) smoked more than 20 cigarettes a day and their mean total exposure was 53 pack-years. Corresponding figures for those with p53-negative tumors were 21 (46%) smoking more than 20 cigarettes a day with a mean total exposure of 36 pack-years. There was, however, no difference between the groups in total duration of exposure (46 vs. 47 years). Although p53 was expressed more commonly in adenocarcinoma (30% of 10) and squamous carcinoma (28% of 29) than in small cell tumors (10% of 20), this could be accounted for by the smoking history. This study supports a relationship between mutations of the p53-encoding gene associated with overexpression of its protein product and intensity of exposure to cigarette smoke.
Adenocarcinoma↗
The role of the p53 tumor suppressor gene in squamous cell carcinoma of the head and neck.
The objective of this review is to determine whether the p53 tumor suppressor gene plays a role in the development of head and neck cancer. Mutations in the p53 tumor suppressor gene have been shown to be one of the most common genetic abnormalities in human cancers, and the published literature also shows this to be the case in head and neck cancer. Initial investigations into p53 gene expression in head and neck cancers indicated that about 60% overexpressed this gene, which was substantiated by many of the later reports. On analysis of all of the published data, mutations in the p53 gene have been found in exons 4 through 9, with a hot spot in the 238-248 region. Overexpression of p53 gene has not been found to correlate with any of the clinicopathologic parameters or survival (calculated from the date of diagnosis), but it does correlate with a history of heavy smoking and drinking. The p53 gene appears to have a role in both the early and late stages of this disease. Overexpression of p53 was found in the tumors of patients who had stopped smoking 5 to 18 years before their cancer developed; also, the overexpression of p53 has been shown in dysplastic and carcinoma in situ lesions of the larynx. Furthermore, overexpression of this gene was found to correlate with a very poor outcome in a group of patients classified with "end-stage disease." A model is proposed to describe the role of p53 in the development of squamous cell carcinoma of the head and neck.
Carcinoma, Squamous Cell↗
Prognostic significance of oncogenes and tumor suppressor genes in human malignancy.
Recent progress in the field of oncogenes has produced valuable information concerning the molecular and cellular biology of the cancer cell and provided a tool to investigate the process of carcinogenesis. Some oncogenes such as the ras, myc, erbB-2 and abl have been extensively investigated in the progression of carcinogenesis in several types of human tumors. The p53 tumor suppressor gene has recently been shown to play the role of "molecular policeman," and is obviously important in the development of many tumors, as mutations in this gene are the most common genetic abnormalities found in all neoplasias. In certain cases the incidence of aberrant gene expression and genetic alterations of oncogenes and tumor suppressor genes have been shown to be important in the progression of these cancers and may be of use as prognostic indicators and form the basis for a successful therapy.
Animals↗
Expression of the cell-cell adhesion molecule E-cadherin in squamous cell carcinoma of the head and neck.
The expression of the cell-cell adhesion molecule E-cadherin has previously been shown to be reduced in poorly differentiated squamous cell carcinoma of the head and neck and absent in nodal metastases. Twenty-eight patients with previously untreated squamous cell carcinoma of the head and neck, 22 of whom had nodal metastases at presentation, were investigated for E-cadherin expression using the monoclonal antibody 6F9, specific for human E-cadherin. Reduced expression was seen in the poorly differentiated primary tumours, compared with well differentiated tumours, but this trend was not statistically significant. E-cadherin expression was present at a reduced level in nodal metastases. It was also noted that, where both the primary tumour and corresponding nodal metastasis were investigated, E-cadherin expression was identical for both samples. The degree of E-cadherin expression did not correlate with survival. These data confirm a reduction in E-cadherin expression in poorly differentiated tumours. There was no correlation between E-cadherin expression and any of the host, tumour and treatment factors associated with malignancies of the head and neck region.
Antibodies, Monoclonal↗
Non-squamous malignancy in lymph nodes: the occult primary.
The present study presents 105 patients seen at a head and neck specialist clinic with a neck gland which subsequently proved to be a non-squamous malignancy. Of the 105 patients, 50 patients were eventually found to have a tumour in the head and neck region, 30 to have a distant primary and in 25 no primary site was ever found. The majority of patients were diagnosed in the clinic after careful examination and most of the remainder were diagnosed during endoscopy/biopsy. Chest radiography was the most useful investigation for diagnosing primary tumours of the lung. The 5-year-survival for the whole group of 105 patients was 28% (95% CI 17-39). The 5-year-survival for the head and neck primary tumour group was 44% (95% CI 25-60). The median survival of patients with a distant primary tumour was only a 6 months, there was one 5-year-survivor. The median survival for those in whom the primary was never discovered was 18 months. However, a reasonable proportion of these patients survived, five being alive at 5 years. The difference between survival for the three groups was statistically significant (P < 0.001). The most common histological type was undifferentiated/anaplastic tumours (37 out of 105) and this was followed by adenocarcinoma (33 out of 105). There was a significant difference in the survival between these two groups (chi 2 = 2.02, d.f. = 1, P = NS). Multi-variate analysis suggested that survival was better in the older age group and was affected by histology (P = 0.0093, P = 0.0332 respectively). The present study suggests that the treatment of patients in whom the primary site is eventually found to be in the head and neck region is rewarding with the same survival as a similar group of patients with squamous cell carcinoma. Sixty of the group of 105 patients had excision biopsies of the neck node and this did not affect survival.
Adenocarcinoma↗
Overexpression of p53 gene in head-and-neck cancer, linked with heavy smoking and drinking.
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Alcohol Drinking↗
Multiple cytogenetic aberrations in squamous cell carcinomas of the head and neck.
Chromosomal abnormalities in short term cultures have been investigated in 10 squamous cell carcinomas of the head and neck. Of these tumours, three demonstrated clonal chromosomal abnormalities, two showed random abnormalities and 5 patients' tumours had normal karyotypes. The 5 patients with aberrant karyotypes were all from previously treated tumours, of these, 4 patients had received radiotherapy and 1 surgery. On analysis of the three clonal tumours, two were found to be polyclonal, each with five separate clones. 116 breakpoints were demonstrated from the clonal data of these tumours, and all of the chromosomes were involved, apart from number 18. In this study we found three or more breakpoints at sites 1p36, 9q32 and 11q23. 1 of the patients investigated showed a clonal abnormality involving a breakpoint at the 11q13 site, with a further 2 patients having breakpoints at 1p22--sites previously reported to have marked clustering of cytogenetic abnormalities in oral cancer patients. Only further studies will demonstrate whether the breakpoints found are of clinical significance.
Carcinoma, Squamous Cell↗
Oncogenes and tumour-suppressor genes in squamous cell carcinoma of the head and neck.
Cancer is now considered to be a multi-hit process which involves a number of aberrant genetic events culminating in malignant transformation. In squamous cell carcinoma (SCC) of the head and neck the action of both oncogenes and tumour-suppressor genes has been identified during the course of the disease. Cytogenetic analysis of these carcinomas has demonstrated chromosomal breakpoints, particularly in the regions of 1p22 and 11q13 together with frequent amplification of the proto-oncogenes in the 11q13 amplicon; int-2, hst-1 and bcl-1. Ras mutations have been infrequently identified in the Western World whereas ras over-expression has been a common finding and may be associated with the early development of head and neck cancer. C-myc over-expression appears to correlate with a poor prognosis for these patients. The tumour-suppressor gene p53 is also thought to be involved in the development of SCC in head and neck tumours and its aberrant expression is associated with a history of heavy smoking and heavy drinking. E-cadherin, a putative tumour-suppressor gene is down-regulated in poorly differentiated head and neck SCC and maybe important in nodal metastasis. A recent study has indicated that the Human Papilloma Virus (HPV 16 and 33) has a role in the aetiology of tonsillar carcinomas and HPV has been shown to produce transforming proteins which bind to and inactivate the p53 tumour suppressor gene. This evidence suggests that the possibility of a viral mechanism for the development of SCC in the head and neck should be considered. This paper proposes a series of genetic events to explain the development of SCC of the head and neck.
Cadherins↗
A phase II study of cisplatinum versus cisplatinum + nifedipine in end-stage carcinoma of the head and neck.
Forty patients with end-stage carcinoma of the head and neck were admitted to a randomized double blind trial with cisplatinum in one arm and cisplatinum + nifedipine in the other. Nifedipine, a calcium channel blocking drug, inhibits the effect of acquired multidrug resistance in animal models. In the present study the addition of this agent had no effect on either response rate or survival in end-stage carcinoma of the head and neck. It is concluded that adding nifedipine to cisplatinum serves no useful purpose in the treatment of end-stage carcinoma of the head and neck.
Antineoplastic Combined Chemotherapy Protocols↗
Low levels of ras p21 oncogene expression correlates with clinical outcome in head and neck squamous cell carcinoma.
We have previously demonstrated that the Ha-ras and the Ki-ras oncogenes are overexpressed in squamous cell carcinoma of the head and neck. In this study we have used the Y13-259 monoclonal antibody to p21 ras to determine if expression of the ras oncoprotein correlates with any of the clinico-pathological parameters or with survival in 69 patients with squamous cell carcinoma of the head and neck. Forty-four specimens were from patients with previously untreated tumours and 25 from patients with previously treated disease. We have found a correlation between low levels of ras expression and the disease-free survival period in patients with previously untreated tumours. Three per cent of the patients with ras negative staining were alive 60 months after diagnosis, whereas 54 per cent of the patients with positive staining were still alive after the same time period (P less than 0.05).
Animals↗
Elevated P53 expression correlates with a history of heavy smoking in squamous cell carcinoma of the head and neck.
Expression of the tumour suppressor gene p53 was examined in squamous cell carcinoma of the head and neck using two p53 antibodies, PAb 421 and PAb 1801. Elevated p53 expression was found in 67% of the 73 patients investigated. P53 expression was not found to correlate with whether the patient had been previously treated or not, nor any of the clinico-pathological parameters. However a correlation was found between the patients smoking history and positive p53 staining. Six out of seven non-smokers did not express p53 whereas 29 of 37 heavy smokers were found to have elevated p53 expression (P less than 0.005). Also, of a group of ten patients who had given up smoking more than 5 years ago, nine had elevated expression. Epidemiological studies have shown a correlation between heavy smoking and head and neck cancer. The present study indicate a genetic link for this correlation.
Carcinoma, Squamous Cell↗
Immunohistochemical analysis of the expression of the c-myc oncoprotein in human stomach cancers.
In an immunohistopathological study, we have used the specific monoclonal antibody myc 1-9E10 to the c-myc oncoprotein in 88 gastric carcinomas (22 gastric biopsies and 66 gastrectomies for cancer). Positive myc p62 immunoreactivity was shown in 48 (55%) cases with moderate or intense staining. The remaining 40 cases exhibited negative or equivocal staining. Normal stomach mucosa was generally nonreactive, with the exception of parietal cells. Elevated c-myc expression was not found to correlate with histological differentiation or in patients with metastases in one or more perigastric lymph nodes. A correlation was found between the level of c-myc expression and the stage of the disease, (p = 0.04); positive c-myc staining was found in 0/4 early gastric cancers and in 48/84 with advanced disease. Also, an association was found between the elevated c-myc expression and depth of invasion (p = 0.1; 0/4 mucosa and submucosa, 2/6 muscularis propria and 25/47 serosa). The c-myc monoclonal myc 1-9E10 may therefore be of use as a marker of advanced disease and depth of invasion in stomach cancer.
Adenocarcinoma↗