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Biomedical subjects

P Mirejovský

Publications and source records attributed to P Mirejovský.

At least 19 recordsLinked to original sources

Expression of cyclin D1, Ki-67 and PCNA in non-small cell lung cancer: prognostic significance and comparison with p53 and bcl-2.

Uncontrolled cell proliferation is the hallmark of malignant tumours. Thus, the proliferative potential of tumour cells is an important prognostic factor. However, evaluation of the prognostic significance of the expression of proteins involved in regulation of cell proliferation remains controversial. In the present study, expression of Ki-67, PCNA and cyclin D1 was estimated in a group of 89 surgically resected non-small cell lung carcinomas using immunohistochemistry. The results were compared with expression of bcl-2 and p53 and with clinicopathological parameters including patients' survival. Ki-67 and PCNA were found to be moderately and highly expressed in 39% and 44% of the tumours, respectively. There was a strong correlation between Ki67 and PCNA expression. Forty five of 88 tumours (51%) showed overexpression of cyclin D1. Surprisingly, cyclin D1 was mainly localized in the cytoplasm and only a small group of tumours (9/88, 10%) showed nuclear staining as well. Bcl-2 and p53 expression was observed in 69% and 30% of the tumours, respectively. All these markers were found to be independent of clinicopathological parameters, except for Ki-67 and bcl-2 expression, which was associated with squamous cell carcinomas. It is concluded that none of the markers that were studied can be used as an independent prognostic factor, whereas the following combinations of markers may have favourable prognostic value: p53 positivity and low Ki-67 expression, p53 positivity and lack of cyclin D1 expression, bcl-2 positivity and low Ki-67 expression, and lack of cyclin D1 expression and low Ki-67 expression.

Adenocarcinoma↗

[Expression of p53, p21 and bcl-2 in prognosis of lung carcinomas].

Expression of suppressor genes 53 and bcl-2 as well as of protein p21 (partly induced by p53 gene) was analyzed in a group of 77 resection specimens and bronchial excision of lung carcinomas (of all basic histological types--squamous cell, neuroendocrine, adenocarcinoma, undifferentiated). Simultaneously the relation of tumor immunophenotype and level of differentiation, cell death and 2-year-survival of patients was evaluated. Gene p53 showed non-only an expected strong expression in squamous cell carcinomas but especially in adenocarcinomas, which were newly characterized by exceptional hyper-expression of p53 in lowly differentiated variants. Expression level of protein p21 and gene p53 was parallel only in adenocarcinomas and undifferentiated carcinomas but discordant in squamous cell and neuroendocrine carcinomas. Positivity of p21 slightly prevailed in well-differentiated variants of the histological types but an exceptional positivity was found even in all the undifferentiated carcinomas. Gene bcl-2 revealed a paradox of strong expression in lowly differentiated neuroendocrine and undifferentiated carcinomas. The level of bcl-2 expression in squamous cell carcinomas was found higher than in references. Among tumors with cell death there was an inverted relation of bcl-2 and p53 expression (high/low) in neuroendocrine carcinomas but both of them were mostly negative in squamous cell carcinomas. A more frequent 2-year-survival of squamous cell carcinomas was verified for bcl-2 positive tumors and newly for p53 positive squamous cell carcinomas. Evaluation of the expression of p53, p21 and bcl-2 in lung carcinomas is so equivocal that its prognostic usage was found to be only complementary to the direct immunohistochemical investigation of the growth activities.

Biomarkers, Tumor↗

Cytokeratins and lung carcinomas.

BACKGROUND: Recently, cytokeratins (CK) were studied as tumor markers for many carcinomas. In lung cancer they appeared to be useful in distinguishing primary from secondary tumors, in histological typing as well as in evaluating patient's prognosis. However, the results have yet to be conclusive. In this study, expression of CK7, CK10/13, CK18, CK19, CK20 was investigated in a group of 72 surgically resected specimens of lung including 31 adenocarcinomas, 30 squamous cell carcinomas and 11 neuroendocrine carcinomas. Cytokeratin immunophenotypes were analyzed in comparison to histological characteristics of tumors, TNM stages and patients survival. RESULTS: CK7, CK10/13 and CK18 can be used in distinguishing the lung adenocarcinomas from the lung squamous cell carcinomas: CK7(+), CK10/13(-), CK18(+) for adenocarcinomas; CK7(-), CK10/13(+), CK18(-) for squamous cell carcinomas. Relatively higher CK7 and CK18 immunostaining rates of the squamous cell carcinomas with high keratinization, with high percentage of dead cells and with late stages of disease suggested their prognostic significance but it was not confirmed when comparing different survival groups. Both adenocarcinomas and squamous cell carcinomas were stained strongly with antibody against CK19 (90.3% and 86.7% respectively) but much less with anti-CK20 antibody (9.7% and 3.3% respectively). In general, neuroendocrine tumors of the lung were non-reactive for these cytokeratins except CK18, among them all carcinoid tumors expressed CK18 abundantly.

Adenocarcinoma↗

[A large metastasis of colorectal carcinoma--case report].

The authors present the case-history of a female patient four years after a low resection on account of carcinoma of the rectum who developed a large secondary in the abdominal wall. After its radical resection the patient is free from systemic or local manifestations of the basic disease and free from complaints.

Abdominal Neoplasms↗

[Expression of the nm 23 gene in pulmonary carcinomas].

Gene nm 23 may have an antimetastatic function but relevant data in the literature are ambiguous even in the same types of malignant tumors. In a group of 77 lung carcinomas there was not found any relation of gene nm 23 expression to the histologic type of tumor or the level of its differentiation and to the finding of metastases in resected lung materials either. Adenocarcinomas showed a negative relation of nm 23 expression to later occurrence of metastases and to a decreased survival of patients which squamous, neuroendocrine and undifferentiated carcinomas did not. Unexpected low expression or negativity of nm 23 in tumors of little progression and rare high positivities in some lung carcinomas with metastases could be explained by gene nm 23 mutations or inactivation. Results of the study do not encourage the usage of nm 23 as a reliable prognostic marker in lung carcinomas.

Antigens, Neoplasm↗

[Clinicopathologic correlation of interstitial pulmonary processes].

"Not-specified interstitial" lesions represented mostly cryptogenic fibrous alveolitis, extrinsic allergic bronchioloalveolitis prevailed among "disseminated" lesions, "infiltrative" lesions were proved to be extrinsic alveolitis or disseminated carcinoma. Among more definitely formulated suppositions of the clinician, cryptogenic alveolitis was proved in more then 50% of cases often modified by extensive fibrosis, organized pneumonia, cholesterol pneumonia or minute desquamative pattern. A similar relation of diagnostic correctness was found in allergic bronchioloalveolitis suprisingly often modified again by fibrosis and cholesterol pneumonia. Valid diagnoses were found in sarcoidosis, presumed Goodpasture syndrome harboured only pneumoconiotic stigmatization. In brief: Bioptical diagnosis nearly always replaced a vague clinical evaluation whereas definite nosological formulations were proved, turned more exact or changed in equal proportions, biopsy was not found contributory but in two cases.

Biopsy↗

[Sarcomatous hepatocellular carcinoma].

Atypical variants of liver carcinomas may represent diagnostic pitfalls when compared with classical types. We described two cases of unusual hepatocellular carcinoma with sarcomatoid pattern. Both were large tumors in elderly people. Their immunohistochemical investigation showed a coexpression of various epithelial and mesenchymal markers. There were positivities of antibodies against cytokeratin, actin and desmin in the first case, against cytokeratin, chromogranin and actin in the second case and against EMA and A1AT in both of them. Such a tumor was not found either in five year bioptic and four year necroptic archival material or in the Hlava Institute histopathological collection. The frequency of the tumor was about 4% of all hepatocellular carcinomas according to the literature.

Actins↗

[Visceral and cutaneous leishmaniasis].

Two cases of kala azar and 5 cases of cutaneous leishmaniasis were found in bioptic files from previous 50 years in Hlava Institute of Pathology in Prague, 4 of them were cumulated in 1994 and 1995. All cases followed short stays in Mediterranean or Caribbean area. The latest kala azar was identified from bone marrow trephine biopsy and subsequently, leishmanias were also found in an inapparent hepatopathy. In cutaneous cases, a fibrinoid vasculitis was observed in addition to accumulation of leishmanias laden macrophages and tuberculoid granulomas.

Humans↗

Medulloepithelioma in a cat.

Castrated male of European cat, bastard, 16 month-old suffered from a grayish-pink tumour in the anterior chamber of the right eyeball in the course of last six months. After enucleation, the eye was examined by histology, immunohistochemistry (NSE, NPF, S-100 protein) and electronmicroscopy. The tumour was classified as malignant medulloepithelioma. Existence of neuroblastoma in animals and frequency of neuroblastoma and medulloepithelioma in humans and animals is discussed.

Animals↗

[Lectins in pulmonary adenocarcinomas].

A relatively specific binding of lectins to various glycids enabled authors to evaluate the exosecretion characteristic of lung carcinomas closer than by HE, investigation of mucins and immunohistochemical epithelial markers. The main subtypes of lung adenocarcinomas (usual of acinar, tubulopillary cubocellular or cylindrocellular, solid with mucus production), pseudosarcoma, large cell and undifferentiated carcinomas from 9 bioptical samples were therefore compared as to binding of 5 lectins with preferential affinity to glucose/mannose (CON A), acetylglucosamin (WGA) and acetylgalactosamin (PNA, RCA, HPA). All the subtypes of adenocarcinoma as well as undifferentiated carcinoma showed a strong binding of bean lectin (CON A) and a slighter binding of ricinus (RCA) and wheat germ (WGA) lectins. Binding of Helix pomatia lectin (HPA) was nearly parallel to that of CON A even in large cell carcinoma (without mucin positivity)-except in undifferentiated carcinoma (in HE reminding of squamous carcinoma but CK negative). Peanut lectin (PNA) binding correlated with the production of acid glycosaminglycans and its lacking might serve as an indirect sign of Clara cell origin in some cubocellular bronchioloalveolar carcinomas which was otherwise difficult to prove. Lections mostly did not bind to mucus vacuoles and cytoplasmic granulary positivities represented secretion granules; marginal membranous positivities represented glycocalyx or lipoproteinaceous layer released by Clara cells in accordance with the expression of EMA. In pseudosarcoma a gradual binding of CON A from sarcomatoid to epithelial areas allowed to evaluate their connection better than according to an expression of cytokreatin.

Adenocarcinoma↗

[Toxic manifestations in the treatment of leukemias and malignant lymphomas].

Toxic effect of chemotherapy was found in 13 dead patients suffering from myeloic leukaemia, Hodgkin disease and malignant lymphoma during past 18 months. Drugs with known toxicity from various sorts of antineoplastic treatment were administered simultaneously or successively what did not allow to differentiate their effects. Clinical symptomatology of the patients comprised respiratory distress syndrome or heart failure which could not be otherwise explained. Pneumopathies prevailed (10 cases) over isolated cardiomyopathies (3 cases), their concurrence was found in 3 other cases. Pneumopathies were mostly (9 cases) characterized by diffuse alveolar damage, by often bizarre proliferating type II pneumocytes and capillary thrombi. Simultaneous organizing processes (7 cases) in alveoli and bronchioli were present and sometimes combined with interstitial lung fibrosis; a single secondary alveolar lipoproteinosis was combined with intraalveolar organization. Cardiomyopathies were mostly characterized by irregular cardiocyte hypertrophy and focal fibrosis, sometimes by distended and waved or vacuolated cardiocytes. Toxic lesions are reversible as usual and risky treatment modalities found out by pathologist are to be early modified.

Adult↗

[Combined small cell and "adenoid cystic" carcinoma of the uterine cervix].

Cervical carcinoma in a 49-year-old woman was resected and found to spread into parametrium. It consisted of a unique combination of adenoid cystic, squamous and small cell neuroendocrine structures. Small celled part revealed positivity with chromogranin A and neuron-specific enolase, neuroendocrine granules were argyrophilic and about 130 nm in diameter. Adenoid cystic and squamous parts were lacking of unambiguous neuroendocrine or myoepithelial differentiation. The patient died in 27 months due to generalization but only a small cell carcinoma without any heterogeneity was found in autopsy. Small cell and adenoid cystic carcinomas are rare and more malignant than usual cervical carcinomas.

Carcinoma, Adenoid Cystic↗

[Relapsing polychondritis--ultrastructure in 2 additional cases].

A 37-year-old woman and a 74-year-old man with typical clinical history of relapsing polychondritis enabled electron microscopical analysis of various cartilages (ear, nasal septum, rib). Apoptotic lesion and degradation of chondrocytes combined not always with changes of their lacunae prevailed in both patients, fragmentation of elastic tissue in the man. Lesions of chondrocytes, a bit varied and asynchronous in intensity were observed as everywhere in a single cartilage as in cartilages from different sites.

Adult↗

[Genodermatoses in fetal skin biopsies].

The risk of serious genodermatoses, i. e. mainly of bullous epidermolyses and keratinization lesions, can be verified only by a prenatal ultrastructural diagnosis. In a group of 23 biopsies of fetal skin the diagnosis of genodermatosis was proved in 10 cases and denied in 10 cases, 3 samples were useless. Discussion points out technological prerequisites of fetal skin biopsy and interpretation problems of ultrastructural diagnostic phenomena in genodermatoses.

Biopsy↗

Possible relationship between abnormal melanosome structure and cytotoxic phenomena in malignant melanoma.

Melanogenesis has been regarded as a hazard for pigment cells which are endangered by reactive quinones and semiquinones generated by this process. Normally the potentially cytotoxic species are confined to melanosomes by a limiting membrane and thus separated from the rest of the cell. Our electron microscopic investigation has demonstrated the presence of abnormal and incomplete melanosomes in human melanomas from epidermal and mucosal sites, in melanoma metastases, and in B16 mouse melanoma. We conclude that significant leakage of reactive melanin precursors including free radical species may occur from aberrant melanosomes in pigmented tumors. This would be expected to be reflected by fully extended physiological scavenging mechanisms, and by local and distant manifestations of cytotoxicity: Among these manifestations is free radical damage to the liver, detected by a thiobarbituric acid-reactive substances assay, in B16 melanoma-bearing mice. The efflux of toxic species from abnormal melanosomes may explain both the observed frequent occurrence of necrosis in melanomas and the therapeutic efficacy of tyrosinase substrates and may also be one of the factors influencing the extent of melanogenuria.

Animals↗

The ultrastructure of respiratory tract tumours.

The study presents the author's experience of 15 years of electron microscopic study of 339 resected respiratory tract tumours, an unusually large group. A dual purpose was pursued: a) to present a systematic analysis of carcinomas which prevailed in the material, and b) to interpret some of the unusual or poorly studied phenomena found in some tumours. The author has been using electron microscopy to study carcinomas since 1973 as a corrective factor giving more precision to routine classification (according to WHO, 1981), on which modern diversified therapy depends. He presents more evidence of the phenotypic heterogeneity of carcinomas, puts aside the histogenetic approach and supports the idea of a common genotypical source of all the programmes of tumour cell differentiation. As regards individual tumours studied by electron microscopy, the author introduced the first ever observation of extrapulmonary neuroendocrine laryngeal carcinoma verified at post mortem examination, a third observation of filamentous bodies in four bronchial carcinoids, and the first observation of a flat epitheloid hemangioma of the larynx. Another case, one of intravascular bronchioloalveolar tumour, is unique for the presence of cytoplasmic crystalline inclusions and leptomeric fibrils which used to be associated with contractile proteins. In a case of bronchioloalveolar carcinoma resembling jaagsiekte, unusual paracrystalline inclusions are demonstrated in a second ever observation, and diagnosed as viral metabolites. Radial cisternae, a peculiar variety of annulate lamellae, found in a lung adenocarcinoma receive closer scruitny because altogether five such cases are on record (two more tumours in the author's archives and another two taken from illustrations to other authors' reports).(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

[The so-called sclerosing hemangioma of the lungs].

A 12-year old girl had a focal density in the lung found by checking CT. Structural features were those of the so called sclerosing hemangioma. Analysis of structure in various methods and of references supported authors' interpretation that lesion represented a late consequence of pecul a obliterative mainly venous process with prevailing plasmacytic feature. Characteristic segmental destructive venous lesion conused segmental obliterat on and hyalinization. Similarity of the lesion to intravascular fasciitis was discussed. Peripheral accumulation of pneumocytes around the lesion seemed to be secondary. To name it pneumocytoma would be unproper and a possibility of vascular tumorous character could not based on respectable analogies. A closer etiopathogenetic specification of the so called sclerosing hemangioma of the lung remains to be accomplished.

Child↗

[Ultrastructural evaluation of pulmonary adenocarcinoma. I. Cytologically homogeneous phenotypes].

A group of 102 lung carcinomas with an ultrastructural evidence of exocrine features comprised 88 adenocarcinomas and 2 adenosquamous carcinomas classified correctly according to the WHO histological typing as well as 12 other carcinomas which had to be re-classified after electron microscopy. Microvilli and secretory granules served as exocrine markers. The microvilli were more specific than granules because of being missing in 15 less differentiated tumours and granules in 45 cases. Microvilli were oriented into intercellular lumina in 65 tumours as well as into intracellular secretion slots in 16 cases, nonpolarized microvilli encirced the circumference of less differentiated cells in 22 tumours. Glycocalyceal bodies were identified not rarely and that was why they did not prove useful in distinguishing primary and secondary lung adenocarcinomas. Electron microscopical classification of adenocarcinomas, more reliable than the light microscopical one, was based on a phenotypical expression of various secretion granules in tumour cells. Phenotypical homogeneity characterized only 56 percent of tumours (57). The two most frequent phenotypes were together mucous cells (5) and dense granule microvillous elements (9) representing serous cells of bronchial glands; cells with apical dense granules but without microvilli (7) represented Clara cells in peripheral carcinomas; type II pneumocytes oftener were normal cells included in tumours (8) than proper tumour cells (2).

Adenocarcinoma↗