Remission of membranous glomerulonephritis after pancreatectomy for pancreatic neuroendocrine neoplasm - a rare coincidence.

The concomitant existence of a non-malignant neuroendocrine tumor (NET) and membranous glomerulonephritis (MGN) is rare. We report a subject with kidney biopsy proven MGN and nephrotic syndrome in which a computerized scan tomography (CT) examination was performed revealing a pancreatic tumor. A pancreatectomy was performed and the tumor was shown to be a non-malignant NET with a malignant potential. Although treatment with corticosteroids was initiated remission of MGN was observed within the next month after pancreatectomy. The rapid remission observed shortly after pancreatectomy pointed to that tumor removal contributed to, and that neither spontaneous nor corticosteroid treatment alone did induce the rapid remission of the MGN. The coexistence of the two disorders NET and MGN is very rare, however. This is the first report on remission of MGN after pancreatectomy for a NET.

Differential cancer predisposition in Lynch syndrome: insights from molecular analysis of brain and urinary tract tumors.

Hereditary non-polyposis colorectal carcinoma (Lynch syndrome) is among the most common hereditary cancers in man and a model of cancers arising through deficient DNA mismatch repair (MMR). Lynch syndrome patients are predisposed to different cancers in a non-random fashion, the basis of which is poorly understood. We addressed this issue by determining the molecular profiles for different tumors from a nationwide cohort of Lynch syndrome families (approximately 150 tumors in total). We focused on some less prevalent cancers, affecting the brain (n = 7) and urinary tract (five bladder and five ureter uroepithelial cancers and four kidney adenocarcinomas), and compared their molecular characteristics to those of the most common cancers, colorectal, gastric and endometrial adenocarcinomas, from the same families. Despite origin from verified MMR gene mutation carriers, the frequency of high-level microsatellite instability in tumors varied between high (100-96% for ureter, stomach and colon), intermediate (63-60% for endometrium and bladder) and low (25-0% for kidney and brain). In contrast to gastrointestinal and endometrial carcinomas, active (nuclear) beta-catenin was rare and KRAS mutations were absent in brain and urological tumors. Compared with other tumors, frequent stabilization of p53 protein characterized urinary tract cancers. Promoter methylation of tumor suppressor genes discriminated the tumors in an organ-specific manner. Our findings suggest that different Lynch syndrome tumors develop along different routes. Uroepithelial cancers of the ureter (and bladder to lesser extent) share many characteristics of MMR deficiency-driven tumorigenesis, whereas brain tumors and kidney adenocarcinomas follow separate pathways.

Is gastric cancer part of the tumour spectrum of hereditary non-polyposis colorectal cancer? A molecular genetic study.

BACKGROUND: Gastric cancer is the second most common extracolonic malignancy in individuals with hereditary non-polyposis colorectal cancer (HNPCC)/Lynch syndrome. As gastric cancer is relatively common in the general population as well, it is not clear whether or not gastric cancer is a true HNPCC spectrum malignancy. AIM: To determine whether or not gastric cancer is a true HNPCC spectrum malignancy. SUBJECTS AND METHODS: The molecular and clinicopathological profiles of gastric cancers (n = 13) from HNPCC mutation carriers were evaluated and compared with the profiles of sporadic gastric cancers (n = 46) stratified by histology and microsatellite instability (MSI) status. RESULTS: This study on sporadic and HNPCC gastric cancers revealed several important universal associations. Loss of heterozygosity in the adenomatous polyposis coli (APC) region was associated with intestinal histology regardless of the MSI (p = 0.007). KRAS-mutations (p = 0.019) and frameshift mutations in repeat tracts of growth-regulatory genes (p<0.001) were associated with MSI tumours being absent in microsatellite stable (MSS) tumours. The average number of methylated tumour suppressor gene loci among the 24 genes studied (methylation index) was higher in MSI than in MSS tumours regardless of histology (p<0.001). Gastric cancers from HNPCC mutation carriers resembled sporadic intestinal MSI gastric cancers, except that MLH1 promoter methylation was absent (p<0.001) and the general methylation index was lower (p = 0.038), suggesting similar, but not identical, developmental pathways. All these lacked the mismatch repair protein corresponding to the germline mutation and displayed high MSI. CONCLUSION: The present molecular evidence, combined with the previous demonstration of an increased incidence relative to the general population, justify considering gastric cancers as true HNPCC spectrum malignancies.

Specialized columnar epithelium of the esophagogastric junction: prevalence and associations. The Central Finland Endoscopy Study Group.

OBJECTIVES: In Barrett's esophagus (BE) normal squamous esophageal epithelium is replaced by specialized columnar epithelium (SCE). BE is related to gastroesophageal reflux disease (GERD) and is a risk factor for esophageal adenocarcinoma. SCE is detected also at normal-appearing esophagogastric junction without BE (junctional SCE). The relationships between junctional SCE, GERD, and cardia adenocarcinoma are obscure and controversial. The aims of the present study were to investigate the prevalence and demographics of junctional SCE and to compare these figures with those reported for BE, and esophageal and cardia adenocarcinoma. A further aim was to examine the association between junctional SCE and GERD, Helicobacter pylori infection, and gastritis. METHODS: One thousand one hundred-nineteen consecutive dyspeptic patients underwent gastroscopy and were enrolled into the study. RESULTS: Junctional SCE was detected in 110 patients (10%). The age-specific prevalence of junctional SCE increased with age. The male:female ratio was 1:1.1. In multivariate analysis, junctional SCE was independently and positively related to endoscopic erosive esophagitis (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-3.1), cardia inflammation (carditis) (OR, 3.1; 95% CI, 1.4-6.8), and age (OR, 1.4 per decade; 95% CI, 1.2-1.6), but not to corpus H. pylori infection (OR, 1.4; 95% CI, 0.7-2.8), antral (OR, 1.0; 95% CI, 0.5-2.1) or corpus (OR, 0.8; 95% CI, 0.4-1.8) gastritis, or intestinal metaplasia of the antral mucosa in stomach (OR, 1.2; 95% CI, 0.7-2.1). In univariate analysis, junctional SCE was, however, significantly more common in patients with antral-predominant atrophic gastritis (20%), compared with those with normal gastric histology (8%, p < 0.001). CONCLUSIONS: Junctional SCE is age related and may therefore be an acquired lesion. It is associated with cardia inflammation and endoscopic erosive esophagitis, but not with H. pylori infection or gastric intestinal metaplasia. Unlike BE and cardia cancer, junctional SCE occurs with similar frequency in men and women.

Apoptotic activity is increased in parallel with the metaplasia-dysplasia-carcinoma sequence of the bronchial epithelium.

A high level of apoptotic activity and an independence of apoptosis from the expression of p53 and bcl-2 have been observed in non-small-cell lung carcinoma. We examined 44 samples of normal, metaplastic and premalignant (i.e. mild, moderate and severe dysplasias and carcinoma in situ) bronchial epithelia to evaluate whether differences in the apoptotic activity could already be seen in the stages preceding squamous cell carcinoma of the lung (SQCLC). Apoptotic cells and bodies were visualized by 3' end labelling. The expression of p53 and members of the bcl-2 gene family, such as bcl-2, bax and mcl-1, were determined immunohistochemically with specific antibodies. The relative number of apoptotic cells and bodies [apoptotic index (AI%)] was already increased threefold as the normal bronchial epithelium changed to squamous metaplasia, and the AIs of the dysplastic lesions were about four times higher than those of the normal epithelium. Apoptosis was significantly associated with cell proliferation, as determined by proliferating cell nuclear antigen (PCNA) immunohistochemistry. However, the extent of apoptosis did not correlate with the expression of p53, bcl-2, bax and mcl-1. We conclude that, in the metaplasia-dysplasia-carcinoma sequence in the lung, the elevation of the AI% is an early event associated with cell proliferation activity, but is independent of the expression of p53, bcl-2, mcl-1 and bax.

Pulmonary adiaspiromycosis in a two year old girl.

A case of disseminated bilateral pulmonary adiaspiromycosis is reported in a two year old Finnish girl. She recovered from this rare infection after treatment with amphotericin B. She is the first human case of adiaspiromycosis in Scandinavia and she is the youngest child with this disease reported so far. Electron microscopy showed that the three layers of the spore wall were not typical; rather, there seemed to be a gradual transition between the main wall zones, which may be split into an indefinite number of thin layers. Varying numbers and thicknesses were seen with different staining methods, and in different spores. Diagnosis relies on recognition of the fungus in a pulmonary biopsy specimen, because there are no reliable serological tests and culture of the fungus is time consuming and not always successful. It was thought that this patient had become infected as a result of contact with soil dust containing the spores in the yard surrounding her home, and as a result of her mother's work in a large garden shop.

Presence of human papillomavirus DNA and abnormal p53 protein accumulation in lung carcinoma.

BACKGROUND: In some carcinomas inactivation of the tumour suppressor gene product p53, either by point mutation or indirectly by the human papillomavirus (HPV), has been suggested as two alternative routes to malignant transformation. To test this hypothesis in lung tumours, 43 lung carcinomas were analysed by in situ hybridisation and polymerase chain reaction (PCR) for the presence of HPV DNA, and the results were compared with p53 protein immunohistochemical analysis. METHODS: The presence of HPV DNA in lung carcinoma was detected by nucleic acid in situ hybridisation for HPV types 6, 11, 16, 18, 31, and 33 using nonradioactively labelled DNA probes. Polymerase chain reaction (PCR) analysis was performed on all cases showing positive HPV DNA labelling by in situ hybridisation and in an additional 13 negative cases. Abnormal nuclear accumulation of the p53 protein was revealed by immunohistochemistry using the avidin-biotin-peroxidase complex method and a CM-1 polyclonal anti-human p53 antibody and a monoclonal mutation-specific Pab 240 p53 antibody. RESULTS: HPV DNA was found by in situ hybridisation in 13 lung carcinomas (30%). In all these cases subtype-specific HPV DNA could also be detected by PCR. Abnormal p53 protein accumulation was seen in 21 of the 43 carcinomas (49%), of which 18 were HPV negative. Twelve (57%) of the CM-1 positive cases were also positive for the mutation-specific antibody Pab 240. There was an obvious inverse relationship between the presence of papilloma viral DNA and abnormal p53 protein accumulation. CONCLUSIONS: p53 plays an important part in the development of lung carcinomas and, in some cases, HPV may contribute to it by binding and inactivating the p53 protein.

p53 protein accumulation and the presence of human papillomavirus DNA in bronchiolo-alveolar carcinoma correlate with poor prognosis.

Accumulation of the tumour suppressor gene p53 product due to a gene mutation is frequently seen in human carcinomas, including lung carcinoma. Another indirect mechanism involving p53 in malignant growth relates to the E6 protein of the human papillomavirus (HPV), which is able to bind and degrade wild-type p53 protein, thus eliminating its tumour suppressor activities. Bronchiolo-alveolar carcinoma (BAC) is a rare type of lung carcinoma. The aim of our study was to examine the occurrence of p53 accumulation and the presence of HPV DNA in BAC. Sections of 22 BACs were immunohistochemically stained using a p53 antibody, CM-1. The presence of HPV DNA in BACs was verified by in situ hybridisation for HPV types 6, 11, 16, 18, 31 and 33 and confirmed by PCR. Thirty-six percent of the tumours showed abnormal p53 nuclear accumulation, and HPV DNA, revealed by in situ hybridisation, was found in 36%. Unexpectedly, only 13% of the type 1 BACs were positive for p53, whereas 45% of the type 2 BACs were positive. During a follow-up of 12-176 months, only 10% of the patients with BACs negative for both p53 and HPV died of the disease, compared with 42% of the patients with either p53 or HPV positivity. No inverse relationship between abnormal p53 protein accumulation and the presence of HPV DNA was found.

p53 protein accumulation in lung carcinomas of patients exposed to asbestos and tobacco smoke.

Primary lung carcinomas often carry mutations in the p53 tumor suppressor gene. Most of these mutations alter the conformation of the p53 protein into a more stable phenotype that makes it immunohistochemically detectable. Asbestos is a carcinogen that can cause deletions in chromosomes and possibly also gene mutations. In this study we examined 70 primary lung carcinomas for p53 protein accumulation using a polyclonal antihuman p53 antibody, CM-1. Patients were interviewed about their occupational and smoking history and classified according to their anamnestical asbestos exposure. Presence of asbestos bodies (AB) was evaluated from histologic samples of peripheral nontumorous lung tissue using both 5-microns-thick sections stained with Perls' iron and 30-microns-thick unstained sections. Abnormal accumulation of p53 protein was found in 36 tumors (51%), more often in patients exposed to asbestos than in patients without exposure (67% versus 40%, p = 0.027). Significant association was also noticed between the accumulation of p53 and the asbestos content of lung tissue: 35% of the p53-positive patients had more than one AB/cm2 compared with 14% of p53-negative cases (p = 0.046). Patients with strongly p53-positive tumors were heavier smokers (57.2 +/- 38.2 pack-years) than patients with p53-negative or lightly positive tumors (38.9 +/- 19.9 pack-years) (p = 0.017). Our findings indicate that both asbestos exposure and heavy smoking can cause abnormal p53 protein accumulation suggestive of mutated p53.

p53 and c-erbB-2 expression in schistosomal urinary bladder carcinomas and schistosomal cystitis with premalignant lesions.

Immunoreactivity for p53 and c-erbB-2 proteins was studied in 31 schistosomal urinary bladder carcinomas and 21 cases of schistosomal cystitis with hyperplastic, metaplastic and/or dysplastic (premalignant) lesions. The results were compared with 30 carcinomas and 21 premalignant lesions of the urinary bladder without schistosomiasis. Abnormal nuclear p53 protein accumulation was found in 17/31 schistosomal and in 15/30 non-schistosomal carcinomas and in 8/21 schistosomal cystitis with premalignant lesions of which five showed hyperplasia. No case of non-schistosomal hyperplasia or squamous metaplasia examined showed p53-positivity. In non-schistosomal carcinomas p53 positivity was significantly associated with tumour grade (grade I-II vs grade III tumours: P = 0.021) and greater age (P = 0.004) while in schistosomal carcinomas no such associations were found. Cytoplasmic membrane-bound positivity for c-erbB-2 oncoprotein was found in comparable percentages in schistosomal and non-schistosomal bladder carcinomas (10%), and in both groups was co-expressed with p53. p53 gene alteration is an important event in the development of both schistosomal and non-schistosomal bladder carcinoma.

p53 immunohistochemistry in transitional cell carcinoma and dysplasia of the urinary bladder correlates with disease progression.

Immunohistochemically detectable p53 protein using a polyclonal antibody (CM-1) was studied in 42 carcinomas of which 11 were grade I, 22 grade II and nine grade III carcinomas. Additionally 14 urothelial dysplasias were studied. In 11 of these a diagnosis of transitional cell carcinoma was established before and in one after the dysplasia diagnosis. Twenty-one out of 42 (50%) cases of transitional cell carcinoma were positive for the p53 protein. Eleven out of 14 (78%) dysplasias and 10/12 (83%) related carcinomas were p53 positive. One out of 11 grade I (9%), 12/22 grade II (55%) and 8/9 grade III (89%) tumours showed positivity for p53. There were significantly more p53 positive cases in grade II-III tumours than in grade I tumours (P = 0.004). There were significantly more p53 positive cases in stage T2-T4 tumours than in stage T1 tumours (P = 0.035). In only one case among the 11 dysplastic lesions following the treatment of a carcinoma the dysplastic lesion was p53 negative while the preceding carcinoma was p53 positive. All dysplasias and 28 carcinomas were also immunostained for laminin and type IV collagen to evaluate the continuity of basement membranes (BMs). Clearly disrupted BMs were observed only in grade III carcinomas. These cases showed the most p53 immunopositivity. The results show a strong association of p53 staining between dysplasias and transitional cell carcinomas of the urinary bladder indicating that these lesions might share similar p53 changes. The correlation to grade, clinical stage and to disrupted BM suggests that p53 mutations may be associated with the evolution of aggressive growth characteristics in transitional cell carcinomas or, alternatively, that p53 positive tumours of a more aggressive type from the start. Whether p53 staining can be used as an adjunct in the assessment and follow-up of epithelial changes of patients treated for a p53 positive bladder carcinoma deserves to be studied.

Tenascin immunoreactivity in lung tumors.

The distribution of tenascin immunoreactivity was analyzed in nonneoplastic lung tissue, benign lung tumors, and different types of lung carcinomas. In nonneoplastic lung tissue, tenascin could be observed in the basement membranes of the bronchial epithelium and endothelial cells, smooth muscle cells, and bronchial cartilage. Strong tenascin immunoreactivity was seen in the stroma of all the carcinomas of various histologic types. The staining intensity was stronger in the stroma of squamous cell carcinomas than in the stroma of the other types of lung carcinomas. In 10 of 27 squamous cell carcinomas, a granular intracytoplasmic reactivity could also be observed in a subpopulation of tumor cells. Similar intracytoplasmic reactivity was observed in 2 of 27 adenocarcinomas and in both adenosquamous carcinomas. In other types of lung tumors, individual cells did not have intracytoplasmic tenascin, except for one case of leiomyoma, which showed a weak, linear, intracytoplasmic tenascin reactivity. In lung hamartomas, tenascin could be seen in the cartilaginous component of the tumor and in the areas of basement membranes of the bronchial epithelium. In the carcinoid tumors, the stroma displayed a faint positivity for tenascin. These results show that tenascin is widely expressed in the stroma of lung carcinomas. A proportion of lung carcinomas also expressed intracytoplasmic tenascin immunoreactivity, suggesting that tumor cells may be able to synthesize tenascin. In the lung, tenascin positivity is not, however, restricted to malignant neoplasms, as evidenced by the presence of tenascin in nonneoplastic lung parenchyma and in some benign lung tumors.

p53 and c-erbB-2 protein expression in adenocarcinomas and epithelial dysplasias of the gall bladder.

In this study we investigated immunohistochemically the expression of p53 and c-erbB-2 proteins in 30 gall bladder adenocarcinomas, one carcinoma in situ, eight gall bladder epithelial dysplasias, and four cases of chronic cholecystitis. p53 expression could be found in 14 (47 per cent) adenocarcinomas and in two out of eight epithelial dysplasias. There were significantly more p53-positive grade II-III tumours than grade I tumours (P = 0.032 according to Fisher's exact probability test). c-erbB-2 expression was found in three (10 per cent) adenocarcinomas, but all dysplasias were c-erbB-2-negative. All three c-erbB-2-positive cases were also p53-positive. The results indicate that p53 mutations and c-erbB-2 gene alterations play a role in the neoplastic transformation of gall bladder epithelial cells. Co-expression of p53 and c-erbB-2 suggests that alterations of these genes might act in concert in the neoplastic transformation. The occurrence of p53 expression in gall bladder dysplasias suggests that p53 mutations could be an early event in the evolution of some gall bladder carcinomas, as has been suggested for some other types of tumours, such as lung squamous cell carcinomas.

Concurrent p53 expression in bronchial dysplasias and squamous cell lung carcinomas.

We analyzed the p53 protein immunohistochemically in bronchial dysplasias or squamous cell carcinomas in situ and in squamous cell lung carcinomas occurring in the same patients. The polyclonal antibody used (CM-1) is directed against the wild-type p53 protein, but also recognizes the mutated p53 in formalin-fixed and paraffin-embedded sections. To study the integrity of basement membranes (BMs) and the possible invasion of the dysplastic epithelium, immunostainings for the BM proteins laminin and type IV collagen were used. Nine of the 17 dysplasias showed p53 protein expression (53%); it was significantly more often seen in severe dysplasias and carcinomas in situ than in mild or moderate dysplasias (P = 0.04). The p53 antigenicity was generally located in the basal part of the epithelium. The BMs beneath mildly dysplastic epithelia were continuous. In contrast, those under moderately or severely dysplastic epithelia showed occasional disruptions. p53 protein expression was also found in dysplastic epithelium above a continuous BM suggesting an ominous process before signs of invasion. Twelve of the 17 squamous cell carcinomas showed p53 protein expression (71%). There was a significant concurrent p53 expression in bronchial dysplasias and their related squamous cell carcinomas (P = 0.009), so that all nine cases of p53 positive bronchial dysplasia also showed p53 positivity in the associated squamous cell carcinomas. These findings indicate that p53 protein expression is possible in premalignant bronchial lesions, and suggests that the p53 expression could, at least in some cases, be an early event in the development of a squamous cell carcinoma of the lung.

p53 immunohistochemistry in malignant fibrous histiocytomas and other mesenchymal tumours.

In this study we analysed by immunohistochemistry the expression of p53 protein in 14 malignant fibrous histocytomas (MFHs), 22 other types of sarcoma (eight leiomyosarcomas, four rhabdomyosarcomas, four liposarcomas, two fibrosarcomas, two chondrosarcomas, one malignant schwannoma, and one dermatofibrosarcoma protuberans), and 25 non-malignant mesenchymal lesions (eight dermatofibromas, four cases of nodular fasciitis, three leiomyomas, three fibromatoses, two epithelioid.leiomyomas, two neurofibromas, one schwannoma, one myositis ossificans, and one giant cell tumour of tendon sheath). Four MFHs and nine other types of sarcoma (four leiomyosarcomas, two chondrosarcomas, one liposarcoma, one fibrosarcoma, and one dermatofibrosarcoma protuberans) showed nuclear positivity for p53. Of the benign soft tissue lesions, p53 positivity was observed in two fibromatoses, one nodular fasciitis, and one dermatofibroma. The number of p53-positive cells in these benign lesions was considerably smaller than that in most of the p53-positive sarcomas. The p53 positivity in MFHs and other types of sarcoma indicates that p53 gene alterations may play a part in the neoplastic transformation of these tumours. The occurrence of p53 positivity in benign mesenchymal lesions suggests that sometimes p53 protein may accumulate in cells without an associated malignancy. Because of this, p53 immunoreactivity cannot, by itself, be used as a criterion of malignancy. According to our results, p53 positivity in over 1 per cent of tumour cells in mesenchymal lesions favours malignancy.

Evidence by in situ hybridization that c-erbB-2 proto-oncogene expression is a marker of malignancy and is expressed in lung adenocarcinomas.

In order to identify potential markers of malignancy in diagnostic respiratory cytopathology, c-myc and c-erbB-2 proto-oncogene expression was studied in fine needle aspirates from 14 consecutive fresh operation tissue samples (after surgical removal) representing lung tumors and a variety of other cell samples by in situ hybridization of 35S-labeled antisense and sense RNA c-myc and c-erbB-2 specific proto-oncogene probes. All 14 lung tumors showed c-myc expression and eight also showed c-erbB-2 expression. On average, the c-myc expression was about 4 times higher than that of c-erbB-2 (P less than 0.001). c-erbB-2 expression, confirmed also as a cytoplasmic membrane-bound reactivity by immunohistochemical stainings for c-erbB-2 oncoprotein, was significantly related to adenocarcinoma (P less than 0.025), whereas increasing tumor size correlated significantly with increasing c-myc expression (P less than 0.05). On average, all the tumor cell lines showed 2-fold expression of c-myc compared with the lung tumors (P less than 0.025). c-erbB-2 expression was found in six of 11 cell lines. High c-myc proto-oncogene expression was also found in broncho-epithelial cells and alveolar macrophages, and a low expression was found in lymphocytes but not in neutrophils, while none of these cells showed c-erbB-2 proto-oncogene expression. Our results demonstrate extensive c-myc proto-oncogene expression in both malignant and non-neoplastic proliferating cells, but not in terminally differentiated cells such as neutrophils. Therefore c-myc expression must also be related to general cell proliferation and not only malignancy per se. In marked contrast, c-erbB-2 proto-oncogene expression was found only in adenocarcinoma cells, and thus can be used as a marker for malignancy in diagnostic respiratory cytopathology.

Comparative analysis of p53 protein immunoreactivity in prostatic, lung and breast carcinomas.

In this study we analysed the expression of p53 protein in a total of 143 carcinomas immunohistochemically. These consisted of 34 prostatic adenocarcinomas, 59 lung and 50 breast carcinomas. In 28 cases, an average of 2-3 additional sections from different tumour areas were analysed. Forty-nine of the 143 carcinomas (34%) showed typical nuclear immunoreactivity by immunohistochemical staining with the p53 antibody CM-1. Two of the 34 prostatic carcinomas (6%) were p53 positive while 25 of the 59 lung carcinomas (43%) and 22 of the 50 breast carcinomas (44%) showed positivity for p53. By grade: 49% of grade III tumours, 36% of grade II and 5% of grade I tumours were p53 positive. There were significantly more p53-positive cases in grade II-III tumours than in grade I tumours (P = 0.001) when all tumours were taken into account. Further, there were significantly more p53-positive cases in grade III than in grade I-II tumours (P = 0.001). In lung tumours there were significantly more p53-positive cases in grade II-III tumours than in grade I tumours (P = 0.018). Similarly, there were significantly more p53-positive tumours in grade III breast tumours than in grade I-II tumours (P = 0.003). The low incidence of p53 positivity in prostate carcinomas suggests that mutations of the p53 gene are not as frequent in the neoplastic transformation of these tumours as in lung or breast carcinomas. The association of p53 positivity with tumours of higher grade suggests that p53 mutations lead to tumours of a more aggressive type. The analysis of tumours by multiple sections indicates that p53 positivity is not evenly distributed in tumour tissue. Therefore, analysis of additional tumour areas may reveal positivity some cases, which is not evident if only one section is studied.

Low p53 protein expression in salivary gland tumours compared with lung carcinomas.

Fifty-one salivary gland tumours (23 pleomorphic adenomas, 5 Warthin's tumours, 12 mucoepidermoid carcinomas, 7 adenoid cystic carcinomas, 3 undifferentiated carcinomas and 1 acinic cell tumour) and 27 lung carcinomas (18 squamous cell carcinomas) were analysed immunohistochemically for the expression of p53 nuclear phosphoprotein. Eight out of 51 (16%) salivary gland tumours were p53 positive. Three of these were benign and 5 malignant. All 3 benign salivary gland tumours were pleomorphic adenomas and expressed only occasional nuclear positivity with less than 1% of tumour cells positive. Of the 5 p53-positive malignant tumours, 3 were mucoepidermoid carcinomas and 2 undifferentiated carcinomas. The malignant salivary gland tumours expressed more than 1% of positive nuclei in every case. Seventeen lung carcinomas were p53 positive (63%). Thirteen of these were squamous cell carcinomas, 3 were adenocarcinomas and 1 small cell lung carcinoma. The results show that mutations of the p53 gene may be infrequent in salivary gland tumours when compared with lung carcinomas. The relatively indolent course of some histological types of malignant salivary gland tumours could be associated with the preservation of the non-mutated p53 gene in most of these tumours. The presence of p53 positivity in some pleomorphic adenomas might, on one hand, suggest that p53 gene alterations are also present in these tumours; on the other hand, the accumulation of the p53 protein in these tumours might also be due to some unknown mechanism, not necessarily related to p53 gene mutation.