Exploring the physical activity level and sleep quality among a cohort of healthy females in Egypt: a cross-sectional survey.

OBJECTIVE: In healthy adults, the short-term effects of sleep disruption include disorders of mood, impaired coping ability, deficits in cognition, and reduced quality of life. Increased physical activity may improve sleep duration and quality. The aim was to investigate the physical activity level and sleep quality and their relationship among a cohort of healthy females in Egypt. PATIENTS AND METHODS: We conducted a cross-sectional, self-reported survey. 688 healthy young adult females aged 18-45 years without a prior history of chronic disease were recruited for this study. Demographic data as well as physical activity (International Physical Activity Questionnaire) and sleep quality (Pittsburgh Sleep Quality Index) were collected. RESULTS: 73.5% reported poor sleep quality, which was worse for housewives. 50.4% of participants were either obese or overweight. Approximately 29.7% of the participants were physically inactive. High physical activity levels were associated with higher sleep efficiency compared to moderate physical activity (p=0.01). However, high physical activity resulted in poorer sleep quality overall (p=0.001). CONCLUSIONS: The majority of participants reported poor sleep quality and high levels of physical activity, but the relationship between physical activity and sleep quality was not clear. Poor sleep quality in our study is one of, if not the highest, reported in the literature for a similar age range in females.

Role of lung ultrasound in the assessment of recruitment maneuvers in ventilated preterm neonates with respiratory distress syndrome and its correlation with tracheal IL-6 levels: A randomized controlled trial.

BACKGROUND: This study's aim is to evaluate lung ultrasound (LUS) efficacy in detecting opening and closing lung pressures and its correlation with the tracheal interleukin 6 (IL-6) level. METHOD: This single-blinded randomized controlled study was done at Ain Shams University Children's Hospital neonatal intensive care units, Egypt. It consists of 44 mechanically ventilated preterm neonates with Respiratory Distress Syndrome (RDS). Initial LUS assessment was done followed by randomization to one of 2 groups; group I: 22 patients underwent LUS guided RM and group II: 22 patients underwent non-ultrasound guided RM. Tracheal IL-6 level was measured before and after RM in both groups. RESULTS: The LUS scores showed a sensitivity of 86.7%, specificity of 62.10% and accuracy of 70.45% at the cut-off point >B1 grade. After RM, there was a higher percentage of changes in mean airway pressure (p = 0.03), FiO2 (p = 0.01), PaO2/FiO2 ratio (p = 0.01), and IL-6 (p < 0.01) in group I. The duration of oxygen requirement (6 vs.13.5 days, p = 0.01), invasive ventilation (3 vs.5.5 days, p = 0.03), non-invasive ventilation (2.5 vs. 5 days, p = 0.02) and NICU stay (21.5 vs. 42.5 days, p = 0.03) were less in group I. A positive correlation is found between reaeration score and the duration of O2 requirement (p = 0.002), duration of invasive ventilation (p = 0.001), NICU length of stay (p = 0.002) and negative correlation with PaO2/FiO2 ratio before RM (p = 0.012). The best cut-off point for the reaeration score is >21 with a sensitivity of 75%, specificity of 71.43% and area under the curve of 78.1%. CONCLUSION: LUS-guided RM achieved earlier lowest FiO2, shorter O2 dependency, lesser NICU stay and marked decrease in lung inflammation by decreasing atelectotrauma and shortening the duration of invasive ventilation.

Sclerosing Mucoepidermoid Carcinoma of the Submandibular Gland Presenting as Chronic Sialadenitis: A Case Report and Review of Literature.

Sclerosing mucoepidermoid carcinoma of the salivary gland (SMEC) is a rare subtype of mucoepidermoid carcinoma (MEC), first described in 1987 by Chan and Saw. As far as we are aware, only 30 cases have been published since then. Most cases were located in the parotid gland with some cases described in the submandibular and minor salivary glands. SMEC typically presents as a long-standing mass, with a non-specific enhancing appearance on imaging and is often non-diagnostic on fine needle aspiration, making pre-operative diagnosis very difficult. It is characterised by dense sclerosis within an otherwise typical MEC, frequently with lymphoid proliferation and eosinophils at the periphery. The histological diagnosis of SMEC can be challenging, as the sclerosis may obscure the other morphological features, which can lead to misdiagnosis. Grading can also be difficult, and the prognostic value of grading for SMEC remains unclear. Herein is described a new case of SMEC, presenting clinically as chronic sialadenitis in the left submandibular gland of a 41 year old male. A brief literature review and the issues surrounding diagnosis and grading are also discussed.

A major burn injury in a liver transplant patient.

Immunosuppressive therapy may aggravate the clinical course of a burned patient, primarily affecting wound healing and thus complicating permanent wound coverage. We hereby present the successful management of a 48-year-old female liver transplant recipient with a major burn injury, aiming to elucidate the effects of the patient's immunosuppression on surgical treatment. After admission to the Burns ITU, the patient underwent serial debridement of the burn and coverage with cryopreserved allografts. Despite immunosuppression, no prolonged survival of the allo-epidermis was documented. Nevertheless, a variable degree of vascularized allo-dermis was clinically identified. She subsequently underwent skin autografting and was discharged home with most of the wounds healed. Although there are isolated reports of survival of skin allografts in immunocompromised patients, in our case the allografted skin did not provide permanent wound coverage. However, it permitted a staged surgical management, allowing the immunosuppressive regime to change, the skin donor sites to heal and it also provided a dermal scaffold for successful skin autografting.

Un traitement immunosuppresseur peut obérer l'évolution d'un brûlé, en raison de ses interactions avec la cicatrisation. Nous présentons la prise en charge couronnée de succès d'une patiente de 48 ans transplantée hépatique victime d'une brûlure grave, dans le but de faire le point sur la relation traitement chirurgical/chirurgie du brûlé au stade aigu. Après son admission en réanimation pour brûlés, la patiente a bénéficié de plusieurs séances d'excision/allogreffe. Malgré le traitement immunosuppresseur, les allogreffes ne sont pas restées en place plus longtemps. Cependant, une vascularisation, à un degré variable, de l'alloderme a été cliniquement observée. Elle a pu retourner à son domicile après autogreffes, les brûlures quasiment entièrement cicatrisées. Au contraire de quelques rapports d'intégration d'allogreffes chez des patients immunodéprimés, celles de notre patiente ont été rejetées. Elles ont toutefois tenu suffisamment longtemps pour permettre un changement de l'état immunitaire, la guérison des sites donneurs et le développement d'un sous-sol apte à recevoir les autogreffes.

Dual diagnosis of sarcoidosis and lymphoma.

BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of unknown origin with pulmonary and extrapulmonary manifestations. Worldwide it is most often diagnosed in the third and fourth decades and most often affects Swedish, Danish and black patients. The association between malignancy and sarcoidosis has not been conclusively proven. Cancer can eventually occur in patients who have an established diagnosis of sarcoidosis for example, in sarcoidosis-lymphoma syndrome. Sarcoidosis can also subsequently develop in an oncology patient. There are multiple obstacles to confirming epidemiologically the linkage between sarcoidosis and malignancy. Histological verification and clinical acumen are needed to avoid misdiagnosis. The 18 fluorodeoxyglucose (18-FDG) PET has failed to provide a non invasive diagnostic method to differentiate neoplasia from benign sarcoid lesions and tissue diagnosis is essential before commencing a new therapeutic intervention in patients with lymphoma. METHODS: We report 3 cases of co-diagnosis of sarcoidosis and lymphoma that were seen in an oncology unit in Drogheda, Co. Louth. RESULTS: Our patients varied in the temporal association between the diagnosis of sarcoidosis and lymphoma as well as their demographic characteristics. CONCLUSION: These cases help to demonstrate the need for careful clinical, histological and radiological assessment.

Molecular misreading: a new type of transcript mutation expressed during aging.

Dinucleotide deletions (e.g. DeltaGA, DeltaGU) are created by molecular misreading in or adjacent to GAGAG motifs of neuronal mRNAs. As a result, the reading frame shifts to the +1 frame, and so-called "+1 proteins" are subsequently synthesized. +1 Proteins have a wild-type N-terminus, but an aberrant C-terminus downstream from the site of the dinucleotide deletion. Molecular misreading was discovered in the rat vasopressin gene associated with diabetes insipidus and subsequently in human genes linked to Alzheimer's disease (AD), e.g. beta amyloid precursor protein (betaAPP) and ubiquitin-B (UBB). Furthermore, betaAPP(+1) and UBB(+1) proteins accumulate in the neuropathological hallmarks (i.e. in the tangles, neuritic plaques, and neuropil threads) of AD. As these +1 proteins were also found in elderly nondemented controls, but not in younger ones (<51 years), molecular misreading in nondividing cells might act as a factor that only becomes manifest at an advanced age. Frameshift mutations (UBB(+1)) and pretangle staining (Alz-50 and MC1) seem to occur independently of each other during early stages of AD. We recently detected +1 proteins, not only in proliferating cells present in non-neuronal tissues such as the liver and epididymis, but also in neuroblastoma cell lines. These observations suggest that molecular misreading is a general source of transcript errors that are involved in cellular derangements in various age-related pathologies.

Cathepsin H expression distinguishes oncocytomas from renal cell carcinomas.

BACKGROUND: Because the differential diagnosis of oncocytoma and renal cell carcinoma lacks specificity, new methods supporting correct diagnostic decisions are welcome. MATERIAL AND METHODS: Sixteen cases of renal oncocytoma, and 16 sex-, age-, and stage- matched controls of renal cell carcinoma (T1-2N0M0) were studied. The minimum follow up exceeded ten years. There were no deaths due to neoplasm among oncocytomas, but 4 patient died with metastatic disease among cancer patients. Immunohistochemical staining for cathepsin H was quantified by 3 histoscores. The histoscores evaluated: 1) even cytoplasmic staining of neoplastic cells, 2) granular staining, or 3) total staining. RESULTS: 100% distinction was possible with the even cytoplasmic staining score. Total staining distinguished 87.5%, and granular staining 25% of neoplasms. CAM 5.2 cytokeratin, or vimentin distinguished 84.4% or 56.6% of these tumors, respectively. CONCLUSIONS: Cathepsin H histoscore on even cytoplasmic immunostaining is an excellent method for the distinction of oncocytomas and renal cell carcinomas.

DNA copy number changes in Schistosoma-associated and non-Schistosoma-associated bladder cancer.

DNA copy number changes were investigated in 69 samples of schistosoma-associated (SA) and non-schistosoma-associated (NSA) squamous cell carcinoma (SCC) and transitional cell carcinoma (TCC) of the bladder by comparative genomic hybridization (CGH). DNA copy number changes were detected in 47 tumors. SA tumors had more changes than NSA tumors (mean, 7 vs. 4), whereas the number of changes in SCC and TCC tumors was similar. SA tumors displayed more gains than losses (1.7:1), whereas NSA tumors showed an equal number of gains and losses. Changes that were observed at similar frequencies in SCC and TCC, irrespective of the schistosomal status, included gains and high-level amplifications at 1q, 8q, and 20q and losses in 9p and 13q. These changes may be involved in a common pathway for bladder tumor development and progression independent of schistosomal status or histological subtype. Losses in 3p and gains at 5p were seen only in SCC (P < 0.01) and losses in 5q were more frequent in SA-SCC than in other tumors (P < 0.05). However, changes that were more frequent in TCC than those in SCC included gains at 17q (P < 0.01) and losses in 4q (P < 0.05) and 6q (P < 0.01). Gains and high-level amplifications at 5p were seen only in SA-SCC (P < 0. 01), whereas gains and high-level amplifications with minimal common overlapping regions at 11q13 were more frequently seen both in SA-SCC and SA-TCC tumors (P < 0.01). In addition to the above mentioned alterations, several other changes were also seen at lower frequencies. The variations in the DNA copy number changes observed in TCC, SCC, SA, and NSA bladder carcinomas suggest that these tumors have different genetic pathways.

Role of deoxyribonucleic acid polymerase epsilon in spermatogenesis in mice.

Previous studies on DNA polymerase epsilon indicate that this enzyme is involved in replication of chromosomal DNA. In this study, we examined the expression of DNA polymerases alpha, delta, and epsilon during mouse testis development and germ cell differentiation. The steady-state levels of mRNAs encoding DNA polymerase epsilon and the recombination enzyme Rad51 remained constant during testis development, whereas the mRNA levels of DNA polymerases alpha and delta declined from birth until sexual maturity. Immunohistochemical staining methods, using a stage-specific model of the seminiferous epithelium, revealed dramatic differences between DNA polymerase alpha and epsilon distribution. As expected, DNA polymerase alpha and proliferating cell nuclear antigen showed relatively strong immunostaining in mitotically proliferating spermatogonia and even stronger staining in preleptotene cells undergoing meiotic DNA replication. The distribution of Rad51 was similar, but there was a dramatic peak in late pachytene cells. In contrast, DNA polymerase epsilon was detectable in mitotically proliferating spermatogonia but not in the early stages of meiotic prophase. However, DNA polymerase epsilon reappeared in late pachytene cells and remained through the two meiotic divisions, and was present in haploid spermatids up to the stage at which the flagellum starts developing. Overall, the results suggest that DNA polymerase epsilon functions in mitotic replication, in the completion of recombination in late pachytene cells, and in repair of DNA damage in round spermatids. In contrast, DNA polymerases alpha and delta appear to be involved in meiotic DNA synthesis, which occurs early in meiotic prophase, in addition to functioning in DNA replication in proliferating spermatogonia.

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.

Human papillomavirus DNA and abnormal p53 expression in carcinoma of the urinary bladder.

In this study we analysed 47 bladder carcinomas for the presence of DNA-HPV subtypes 6, 11, 16, 18, 31 and 33 by nucleic acid in situ hybridization, and for the abnormal accumulation of p53 protein by immunohistochemistry. HPV DNA was found in 27/47 (57%) bladder carcinomas, with multiple subtypes in 20 cases. In squamous cell carcinoma (SCC), HPV DNA was only detected in the superficial layer of the neoplastic epithelium and was found mainly in the nuclear compartment. In contrast, in transitional cell carcinoma (TCC), HPV DNA was also found in deeper parts of the tumour. In about half the cases it was mainly found in the cytoplasmic compartment. In SCC, the HPV DNA labelling occurred in koilocytic cells, while no such association was found in TCC. Abnormal accumulation of p53 protein was found in 24/47 (51%) carcinomas. p53 positivity was found significantly more often in SCC than in TCC (p = 0.05). Concurrent HPV positivity and abnormal p53 protein accumulation was found in 18 cases, 14 showing the presence of HPV subtypes 16 and/or 18 DNA. The results demonstrate that HPV DNA occurs widely in urinary tract tumours. Unlike in some other carcinomas, there was no inverse relationship between HPV positivity and abnormal p53 protein accumulation in bladder carcinomas. Thus HPV infection may play a role in the pathogenesis of bladder carcinomas by some mechanism other than inactivation of the p53 protein.

Proliferating cell nuclear antigen but not p53 or human papillomavirus DNA correlates with advanced clinical stage in renal cell carcinoma.

In this study we investigated 56 renal cell carcinomas immunohistochemically for the expression of proliferating cell nuclear antigen (PCNA) and tumour suppressor protein p53. We also analyzed for the presence of human papilloma virus (HPV) DNA subtypes 6, 11, 16, 18, 31 and 33 by in situ hybridization. In carcinomas which showed more than 10% of PCNA positive nuclei there were significantly more cases with invasion (P = 0.032) or metastatic disease (P = 0.047). Nine out of 22 grade III-IV tumours (40.9%) but only six out of 30 grade I-II tumours (20%) showed more than 10% of PCNA positive cells (P = 0.097). Patients with 10% or more PCNA positive cells in kidney tumours had more advanced disease at the time of diagnosis than those showing less PCNA positive cells (P = 0.05). Six p53 positive cases were found among 56 tumours (11%), but only one case had more than 10% positive cell nuclei. The presence of HPV DNA was found in 29 out of 56 cases (52%). Multiple subtypes were found in 19 cases (34%). The most commonly occurring subtypes were 18 and 33. There was no association between PCNA, p53 and the presence of HPV DNA subtypes. Because of the association of PCNA with invasion and metastatic disease, it would be worth while to study PCNA further as a possible marker for aggressiveness of renal carcinomas. Both this study and those concentrated on mutational analysis suggest that p53 is generally not important for the development of renal cell carcinoma. On the other hand, the presence of HPV DNA in these tumours implicates HPV viral infection in the aetiology of renal cancer.

p53 immunohistochemical positivity as a prognostic marker in intracranial tumours.

The frequency and scale of positive p53 immunohistochemistry in 107 intracranial tumours of different types was studied as a possible prognostic marker using a polyclonal antibody CM-1 which detects both the wild-type and mutated p53 proteins. Fifty of the tumours (46.7%) showed nuclear p53 positivity with different percentages of positive nuclei. The positivity was concentrated in glial tumours of which 52.8% were positive. Forty-two of seventy-four astrocytomas (56.8%), 4 of 12 oligodendrogliomas (33.3%), and 1 of 3 ependymomas (33.3%) showed p53-positive nuclei. Cytoplasmic positivity, found in 25 astrocytomas, was always associated with nuclear positivity. Some p53-positive nuclei were seen in 16.7% of the non-gliomatous tumours, but in all cases p53 positivity was seen in less than 1% of the nuclei. The patients with astrocytomas containing more than 5% p53-positive nuclei were younger (mean 27.3 years) (p = 0.016) and their tumours larger in diameter (mean 4.4 cm) (p = 0.05) than those with p53-negative astrocytomas (mean 41.0 years and mean 3.3 cm, respectively). In p53-positive (> or = 1% of nuclei) grade IV astrocytomas, survival time was significantly shorter (mean 7.2 months) than in p53-negative grade IV astrocytomas (mean 15.5 months (p = 0.024). The results indicate frequent p53 expression in intracranial tumours, especially in gliomas. The association of p53 positivity with young age, larger tumour size, and poor prognosis in high-grade astrocytomas suggests that p53 may be involved in the development of more aggressive types of intracranial tumours. According to these results, p53 immunohistochemical positivity may serve as a prognostic marker in high-grade astrocytomas.

Aberrant accumulation of p53 associates with Ki67 and mitotic count in benign skin lesions.

Sixty-two skin samples from patients with a variety of benign disorders (20 cases of psoriasis, 14 cases of chronic dermatitis, 11 seborrhoeic keratoses, 11 cases of lichen planus), and seven normal skin samples, were stained immunohistochemically with a polyclonal antibody (CM-1) to p53, and a monoclonal antibody to Ki67, using the avidin-biotin complex method. p53-positive keratinocytes could be found in most of these lesions. The percentage of p53-positive cells was, however, far lower than usually seen in p53-positive malignant tumours. No p53 reactivity was observed in the normal skin samples. Variable Ki67 reactivity was observed in all skin samples. Overall, the number of Ki67-positive cells was higher in skin samples in which the proportion of p53-positive cells was high (> 0.5% of total epidermal cell population) (P = 0.004). This also applied separately to psoriatic and non-psoriatic lesions (P = 0.028 and P = 0.033, respectively). In cases with > 10% of Ki67-positive cells, there were significantly more mitoses (P < 0.001). This association applied to both psoriasis and the other lesions studied (P = 0.024 and P < 0.001, respectively). The results show that immunohistochemically detectable accumulation of p53 is a frequent finding in non-neoplastic skin lesions. As p53 positivity was associated with the proliferation marker Ki67, the accumulation of p53 is possibly a response to an increased proliferation rate of the keratinocytes in these skin diseases, or alternatively it may be associated with apoptosis.

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.

Application of fine-needle aspiration to the demonstration of ERBB2 and MYC expression by in situ hybridization in breast carcinoma.

Thirteen consecutive fine-needle aspirates of breast carcinoma and five selected breast tumor cell lines were analyzed for ERBB2 and MYC mRNA expression by in situ hybridization. To compare the level of mRNA synthesis with those of gene amplification and oncoprotein synthesis, all tumors were also analyzed by Southern blot analysis, and for ERBB2 also by immunohistochemistry. Expression of ERBB2 mRNA was observed in eight tumors. MYC expression was observed in all tumors studied. Three tumor cell lines expressed both ERBB2 and MYC (SK-BR-3, HeLa, HT-29) and two only MYC (SK-LU-1, HL-60). Only one tumor showed amplification of ERBB2 and two of MYC. In all three cases there was a considerable increase in corresponding mRNA synthesis as detected by in situ hybridization. By immunohistochemistry, four cases showed either patchy areas or uniformly distributed, membrane-bound ERBB2 immunoreactivity. All except one case showed increased ERBB2 mRNA synthesis. There was a clear association between the quantity of ERBB2 mRNA and oncoprotein expression. The results show that in situ hybridization of fine-needle aspiration material is a sensitive method to detect increased expression of the ERBB2 and MYC oncogenes in breast carcinoma. Furthermore, this study indicates that in a majority of cases some other mechanism that gene amplification appears responsible for the increased gene expression. It is also possible that Southern blot analysis is not a sensitive enough method to detect gene amplifications in the heterogeneous breast tumors, which usually also contain stromal tissue. The fact that not all cases with elevated ERBB2 mRNA synthesis were immunohistochemically positive suggests that either immunohistochemistry (after fixation with 10% formalin) is a less sensitive method than in situ hybridization to detect abnormal gene expression or that there are cases in which the oncoprotein synthesis is for some reason depressed, even though there is an increase in gene transcription.

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.