Biomedical subjects
Publications and source records attributed to E Karamitopoulou.
A 6-y-old girl developed fever, soft-tissue mass in the right chest wall, osteomyelitis of the 10th rib and hepatic granuloma. Cat scratch disease was diagnosed by histological examination of the mass and serological tests. The patient was treated successfully with antibiotics and recovered completely, as shown by a 10 month follow-up.
BACKGROUND: Members of the Eph family of tyrosine kinases have been implicated in embryonic pattern formation and vascular development; however, little is known about their role in the adult organism. We have observed estrogen-dependent EphB4 expression in the normal breast suggesting its implication in the hormone-controlled homeostasis of this organ. Since the endometrium is a similarly hormone dependent organ and endometrial carcinoma is thought to result from estrogenic stimulation, we have investigated EphB4 expression in normal human endometrium and during its carcinogenesis. PATIENTS AND METHODS: EphB4 expression was analyzed immunohistochemically in 26 normal endometrium specimens, 15 hyperplasias and 102 endometrioid adenocarcinomas and correlated with clinical and prognostic tumor characteristics. RESULTS: In normal endometrial tissue no EphB4 protein was detected. Strikingly, we observed a drastic increase (P <0.0001) in the number of EphB4 protein-expressing glandular epithelial cells in the majority of hyperplasias and carcinomas. Moreover, we found a statistically highly significant positive correlation between EphB4 expression and post-menopausal stage of the patient (P = 0.007). CONCLUSIONS: These findings indicate that in the endometrium, EphB4 is an early indicator of malignant development and, thus, EphB4 may represent a potent tool for diagnosis and therapeutic intervention.
Sixty biopsy specimens of meningiomas, including 37 benign, 10 atypical, and 13 malignant meningiomas, were examined immunohistochemically using the monoclonal antibodies MIB-1 (a cell proliferation marker), p53, and bcl-2 (two apoptosis-associated markers). Benign meningiomas were subdivided into two groups: group 1, 29 tumors without recurrence; and group 2, eight tumors with recurrence after complete surgical resection. The mean MIB-1 labeling index (LI) values+/-SD were 1.3+/-3.2% for the benign, 9.3+/-6.9% for the atypical, and 15.0+/-16.9% for the anaplastic meningiomas. The mean MIB-1 LI+/-SD in group 1 tumors (n = 29) was 1.06+/-1.15%, and in group 2 tumors (n = 8), 2.3+/-4.76% (P = .028). p53 protein expression was found in 10.8% of the benign (10.34% of group 1 and 12.5% of group 2), 50% of the atypical, and 77% of the anaplastic meningiomas. bcl-2 protein expression was observed in 21.6% of the benign, 20% of the atypical, and 46.1% of the anaplastic meningiomas. Among the benign meningiomas, group 2 tumors expressed significantly more often bcl-2 protein (62.5%) than group 1 neoplasms (10.3%). Our results indicate that (1) in meningiomas, a good correlation exists between histological grading, MIB-1 and p53 protein expression, and (2) in benign meningiomas, the presence of bcl-2 protein expression together with high MIB-1 LI are associated with unfavorable prognosis of the disease.
The immunohistochemical expression of the p53 gene product was examined in 91 colorectal adenomas from patients without (group 1, 50 cases) or with (group 2, 41 cases) concurrent sporadic colorectal carcinoma, and in 15 additional cases of randomly selected carcinomas from group 2 patients. Immunohistochemical reactions were performed with the DO-7 monoclonal and the CM1 polyclonal antibodies, following microwave irradiation of the tissues in an antigen retrieval solution, and the proportion of the immunoreactive cells was semiquantitatively assessed. p53 protein immunoreactivity was present in 46.1% (42, of 91, i.e., 20 out of 50 of group 1 and 22 out of 41 of group 2) and 33% (30 of 91, i.e. 14 out of 50 of group 1 and 16 out of 41 of group 2) of the adenomas using DO-7 and CM1 antibody, respectively. High p53 expression (i.e. immunolabelling of more than 30% of the tumour cell nuclei) was found in 13.2% of the adenomas (12 of 91, i.e. three out of 50 of group 1 and nine out of 41 of group 2; P = 0.025 using the chi 2 test) using the DO-7 antibody, and in 6.6% of the cases (six of 91, i.e. two out of 50 of group 1 and four out of 41 of group 2) using the CM1 antibody. In carcinomas, 80% of the cases (i.e. 12 of 15) were found to express p53 protein with both antibodies. p53 immunoreactivity in colorectal adenomas increased with the degree of dysplasia: only five (17.8%) of the 28 adenomas with mild dysplasia were found to be DO-7 positive, while all of them remained CM1 negative. From the 50 adenomas exhibiting moderate dysplasia, 28 (56%) were DO-7 positive, and 22 (44%) were CM1 positive. Finally, from the 13 adenomas with severe dysplasia, nine (69.2%) and eight (61.5%) were found to be positive with the DO-7 and the CM1 antibody, respectively. Our results indicate that an increased number of group 2 adenomas express p53 protein, when compared with group 1 adenomas, and suggest that a strong correlation exists between p53 protein expression and the degree of dysplasia in colorectal neoplasms.
Forty-five extrahepatic bile duct carcinomas (i.e., tumors of the region proximal to the duct junction, including Klatskin tumors, tumors of the lower mid-region, and tumors of the ampulla of Vater) and 11 gallbladder carcinomas were immunohistochemically examined for p53 protein expression, using the DO-7 monoclonal (mAb) and the CM-1 polyvalent (pAb) antibodies and an antigen retrieval method. Because the DO-7 mAb was found to be significantly more reliable than the CM-1 pAb in detecting p53 immunoreactivity, the immunohistochemical results obtained with the former antibody were used for comparing p53 protein immunoreactivity with tumor site, tumor grade, and survival of patients. Approximately one third (3 of 10) of the proximal tumors were found to express weak p53 immunopositivity, whereas moderate immunopositivity and higher rate (18 of 29) was observed in tumors of the lower mid-region. Finally, moderate and marked p53 immunopositivity was observed in tumors of the ampulla (5 of 6) and gallbladder (8 of 11). In tumors of the lower mid-region of the ampulla and the gallbladder, a significantly higher p53 positivity was noted in high-grade compared with low-grade neoplasms. For the cases in which complete follow-up was available (11 tumors of the low mid-region), median survival of patients with p53-negative tumors was 25.7 months, whereas survival of those with p53-positive tumors was 5.2 months.(ABSTRACT TRUNCATED AT 250 WORDS)
Paraffin-embedded surgical specimens from 136 primary human central nervous system (CNS) tumors, including 50 meningiomas, 24 astrocytomas, 26 anaplastic astrocytomas, 9 glioblastomas, 8 oligodendrogliomas, 4 ependymomas, 1 anaplastic ependymoma, 2 subependymomas, 9 medulloblastomas, and 3 paragangliomas, were immunostained, following microwave processing, using a streptavidin/peroxidase method and the MIB 1 monoclonal antibody (mAb) against the Ki-67 antigen. The following mean Ki-67 labeling index (LI) values +/- SD were found: meningiomas, 2.47 +/- 1.83; astrocytomas, 2.03 +/- 2.03; anaplastic astrocytomas, 12.80 +/- 6.29; glioblastomas, 14.57 +/- 6.77; oligodendrogliomas, 5.06 +/- 4.78; ependymomas, 2.63 +/- 2.58; anaplastic ependymoma, 6.89; subependymomas, 1.79 +/- 1.54; medulloblastomas, 18.77 +/- 9.65; and paragangliomas, 2.19 +/- 2.51. Our findings indicate that while malignant CNS tumors always exhibited high Ki-67 LI values, and benign CNS tumors generally displayed lower values, increased immunoreactivity for Ki-67 epitopes (Ki-67 LI higher than 4) was noted in a number of meningiomas, astrocytomas, ependymomas, oligodendrogliomas and paragangliomas, contrasting with their benign histological features. Further investigations of the Ki-67 immunoreactivity in CNS tumors and systematic correlation with the postoperative follow-up of patients are necessary to determine the value of Ki-67 LI in predicting the biological behavior of CNS neoplasms.
Formalin-fixed, paraffin-embedded liver specimens from 27 2-year-old Wistar rats, including 10 normal livers, 11 hepatocellular adenomas, 2 hepatocellular carcinomas, and 4 cystic cholangiomas, were immunostained using the streptavidin/peroxidase method and the PC10 monoclonal antibody (Mab), which recognizes an epitope on the proliferating cell nuclear antigen (PCNA). The following PCNA labeling index (LI) mean values were found for the above four groups of liver specimens: normal livers, 0.43 +/- 0.31%; hepatocellular adenomas, 1.51 +/- 0.59%; hepatocellular carcinomas, 24.80% +/- 10.28%; and cystic cholangiomas, 0.61 +/- 0.21%. Our findings indicate that PCNA LI clearly separates liver malignancies from other benign liver tumors, as well as from normal, non-neoplastic, liver tissues. Although the mean PCNA LI values seemed to reflect histological grading (i. e. normal, neoplastic benign, neoplastic malignant), overlapping between normal livers and hepatocellular adenomas was observed in five cases (i. e. in 2 normal livers and 3 hepatocellular adenomas, where the PCNA LI values varied between 0.74% and 0.96%). It thus appears that PCNA immunohistochemistry represents a promising tool for investigating liver cell proliferation in laboratory rats, and permits distinguishing between benign and malignant liver parenchymal tumors.
Formalin-fixed, paraffin-embedded surgical specimens from 140 primary human central nervous system tumors, including 51 meningiomas, 26 astrocytomas, 26 anaplastic astrocytomas, 9 glioblastomas, 1 gliosarcoma, 8 oligodendrogliomas, 5 ependymomas, 2 subependymomas, 9 medulloblastomas, and 3 paragangliomas, were immunostained using a streptavidin/peroxidase method and the PC10 monoclonal antibody, which recognizes an epitope on the proliferating cell nuclear antigen (PCNA). The following PCNA labeling index (LI) mean values were found for the above neoplasms: meningiomas, 3.80 +/- 7.35%; astrocytomas, 0.65 +/- 1.03%; anaplastic astrocytomas, 8.46 +/- 7.95%; glioblastomas, 10.26 +/- 11.21; gliosarcoma, 46.34%; oligodendrogliomas, 2.31 +/- 3.59%; ependymomas, 1.12 +/- 2.10%; medulloblastomas, 23.91 +/- 11.95%; and paragangliomas, 2.07 +/- 1.86%. Collectively, our findings indicate that while benign central nervous system tumors generally have low PCNA LI values, consistent over-expression of PCNA epitopes was noted in some examples, especially in a number of meningiomas. Among the malignant neuroectodermal tumors, medulloblastomas were found to have the highest PCNA LI values, corresponding to their histological grade of malignancy, and malignant glial tumors generally displayed significantly higher PCNA LI values, than their benign counterparts. Although in our study mean PCNA LI values seemed to reflect histological grading, large discrepancies were noted in all tumor groups. Our data, therefore, suggest than PCNA immunoreactivity can not be considered reliable for predicting the prognosis of the disease in individual cases.
Formalin-fixed, paraffin-embedded surgical specimens from 137 primary central nervous system tumors, including 26 astrocytomas (21 fibrillary, 1 protoplasmic, 1 gemistocytic and 3 pilocytic), 26 anaplastic astrocytomas, 9 glioblastomas, 1 gliosarcoma, 8 oligodendrogliomas, 4 ependymomas, 1 anaplastic ependymoma, 2 subependymomas, 3 paragangliomas, and 57 meningiomas, were immunostained with the CM1 polyclonal (pAb) and the DO-7 monoclonal (mAb) antibodies against the p53 protein, using the streptavidin/peroxidase method. In addition, two series of 17 and 9 medulloblastomas were also immunostained with the above pAb and mAb, respectively. p53 protein expression was observed in 7 fibrillary astrocytomas, 17 anaplastic astrocytomas, 5 glioblastomas, 1 gliosarcoma, 1 oligodendroglioma, 1 anaplastic ependymoma, and 4 meningiomas with the CM1 pAb. An additional 10 cases (i.e., 3 anaplastic astrocytomas and 7 meningiomas) were found to be p53 protein positive with the DO-7 mAb. Of the medulloblastomas, 8 (of the 17) and 4 (of the 9) were found to express p53 protein with CM1 pAb and DO-7 mAb, respectively. Our results indicate that p53 protein is expressed in a number of central nervous system neoplasms, and suggest that in astrocytic tumors a possible association may exist between p53 protein expression and tumor progression through increasing histological grades of malignancy.
Surgical specimens from 36 medulloblastomas (25 classic and 11 desmoplastic) were studied by peroxidase-antiperoxidase (PAP) immunohistochemistry with antibodies against the class III beta-tubulin isotype (beta-tubulin), synaptophysin, retinal S-antigen (S-Ag), and glial fibrillary acidic protein (GFAP). We found that neoplastic cells expressed beta-tubulin in 91% of the tumors (23 classic and 10 desmoplastic), synaptophysin in 75% (19 classic and 8 desmoplastic), S-Ag in 44% (11 classic and 5 desmoplastic), and GFAP in 11% of medulloblastomas (2 classic and 2 desmoplastic). Synaptophysin and beta-tubulin positivities were observed in undifferentiated neoplastic cells, in cells forming neuroblastic rosettes, and in pale islands, while S-Ag immunopositivity was noted in undifferentiated cells, occasionally in beta-tubulin-negative neuroblastic rosettes, and exceptionally in pale islands. Large pale islands, in two desmoplastic medulloblastomas, exhibited distinct patterns of immunoreactivity to the above markers, suggesting neuronal and glial differentiation in the central area, and intense neuritic development in the peripheral zone. Our findings confirm the predominant capacity of medulloblastoma cells to differentiate along neuronal cell lines and indicate that large pale islands, in desmoplastic medulloblastomas, represent well-organized areas for neuronal and, to a lesser degree, astroglial differentiation. Furthermore, it appears, in our cases, that immunohistochemical features do not represent clear-cut prognostic indicators in patients with medulloblastomas.
An autopsy case of a brain stem ganglioglioma in a 38-year-old male patient with neurological dysfunction of 16-year duration is reported. Immunohistochemical investigation of the tumor was performed using a panel of antibodies against neurofilament protein (NFP), synaptophysin (SY 38), beta-tubulin (TUJ1), neuron specific enolase (NSE), and glial fibrillary acidic protein (GFAP). The value of these markers in the establishment of the diagnosis, as well as the general features, the prognosis and the therapeutic approach of the gangliogliomas are discussed.
Today's stringent requirements for new drugs make it necessary to prove their safety by the use of ever more refined techniques, in particular methods to quantify morphologic findings to determine accurately, for example, the highest non-toxic dose in animal studies or to correlate morphological effects with other parameters. Increased cell proliferation due to subtle cytotoxicity can lead to epigenetic tumorigenicity, which can be recognized early by cytokinetic investigations using bromodeoxyuridine (BrdU) incorporation and/or proliferating cell nuclear antigen (PCNA) expression, or by malignancy-associated nuclear texture changes. Morphometric criteria are also used to increase diagnostic accuracy in experimental animal pathology. The various applications of morphometry in toxicopathology are reviewed, and examples illustrating these applications are presented, most of them unpublished.