Immunohistochemical detection of P-glycoprotein in breast cancer and its significance as a prognostic factor

Overexpression of P-glycoprotein (Pgp) in tumors is one of the major mechanisms which mediates the multidrug resistance (MDR) phenotype. To evaluate the prognostic significance of Pgp in breast cancer, Pgp expression was examined in paraffin-embedded tissue sections of 94 breast cancer specimens by immunohistochemistry. Tissue specimens were obtained by mastectomy without preoperative chemotherapy. UIC2 monoclonal antibody which recognizes an extracellular epitope of human Pgp was employed. Of the 94 breast cancer specimens, 35 (37.2%) were positive for Pgp expression. Pgp expression had no correlation with menopausal or hormone receptor status, axillary lymph node involvement or tumor size. However, a significant correlation was observed between Pgp expression and disease relapse (p = 0.0322). Pgp-positive patients showed a significantly shorter disease-free survival period than Pgp-negative patients by the Kaplan-Meier method (p = 0.0433). These results suggest that immunohistochemical detection of Pgp in breast cancer tissue may have prognostic value after radical operation.     

HLA-DR2 frequency increase in severe aplastic anemia patients is mainly attributed to the prevalence of DR15 subtype

The association between severe aplastic anemia (AA) and DR2 antigen seems to be well established. However, since discrimination between two DR2-associated splits, namely DR15 and DR16, rarely was performed, it remains unclear whether one or both of these subvariants are responsible for AA susceptibility. In this study, we have analyzed the HLA-DR allelic distribution in a group of 37 AA patients of slavic origin from North-Western Russia. The experimental design included PCR-based amplification of DRB-specific sequences, followed by reverse dot-blot hybridization of the biotinylated PCR-product with the set of sequence-specific oligonucleotide probes. HLA-DRB alleles were identified by non-radioactive enzymatic reaction, then standard serological specificities of HLA-DR antigen were estimated according to the WHO nomenclature. Whereas DR15 subtype occurred more often in the patients (23.0% vs. 13.3%, p< 0.05), DR16 split did not show the same tendency. The results, show the overall predominance of HLA-DR2 specificity (DR15+DR16) did not reach statistical significance (24.4% vs.17.5%, p<0.2). Thus, we conclude that repeatedly reported DR2 frequency increase in AA patients is mainly attributed to the prevalence of DR15 subtype.     

Association of Epidermal Growth Factor-related Peptides and Type I Receptor Tyrosine Kinase Receptors with Prognosis of Human Colorectal Carcinomas

The frequency of expression and localization of cripto-1 (CR-1),amphiregulin (AR), transforming growth factor alpha (TGF), epidermalgrowth factor receptor (EGFR) and erbB-2 were examined by immunohistochemistryin 45 carcinomas and adjacent non-involved normal colon mucosa.Thirty (66.7%), 24 (53.3%), 23 (51.1%), 23 (51.1%) and 13 (28.9%)of the 45 carcinomas showed positive staining for CR-1, AR,TGF, EGFR and erbB-2, respectively, whereas 7 (15.5%), 17 (37.7%),15 (33.3%), 20 (44.4%) and 0 (0%) of the corresponding non-involvednormal mucosa specimens were reactive. Among 13 carcinomas withlymph node involvement, 10 (76.9%), 8 (61.5%), 10 (76.9%), 8(61.5%) and 7 (53.8%) exhibited positive staining for CR-1,AR, TGF-, EGFR and erbB-2, respectively. There was a statisticallysignificant association between the frequency of either TGF(P<0.05) or erbB-2 (P<0.05) expression and lymph nodemetastasis. In addition, a signficantly higher frequency ofpositive staining for TGF was observedin Dukes' grade C carcinomas(P<0.05). Finally, significant trends for coexpression ofEGFR and either TGF (P<0.01) or AR (P<0.05) were detectedin carcinomas. These data suggest that AR and TGF may play animportant role in the development of colorectal carcinomas throughan autocrine mechanism involving EGFR, and demonstrate thatTGF and erbB-2 may be more reliable indicators of metastasisor prognosis than CR-1, AR or EGFR in human colon cancers.     

Molecular-pathological Analysis of a Patient with Three Synchronous Squamous Cell Carcinomas in the Aerodigestive Tract

A case of synchronous squamous cell carcinomas in the soft palate,larynx and esophagus is reported, along with findings of molecular-pathologicalanalysis. A biopsy sample from the aryngeal carcinoma revealedwell differentiated squamous cell carcinoma harboring two pointmutations at codons 144 and 148 of the p53 gene but not at codon299, and more than 50% of the cancer cells showed accumulationof p53 protein immunohistochemically. The esophageal tumor,which was moderately differentiated squamous cell carcinoma,showed immunoreactivity for p53 within the nuclei of 25–50%of cancer cells with a missense mutation at codon 299 but notat codon 144 or 148. This cancer also showed immunoreactivityfor transforming growth factor alpha. On the other hand, thepoorly differentiated squamous cell carcinoma in the soft palateshowed negative immunoreactivity for p53 and no point mutationin exons 5 to 8 of the gene. These results suggest that thethree synchronous squamous cell carcinomas arose as independentevents.     

Membrane structures of human oligodendroglioma

Summary Two cases of McArdle's syndrome are reported. One is a classical exaple; the other is unusual because of the in vitro presence of muscle phosphorylase activity. In the latter case. the electronmicroscopic investigation confirmed the diagnosis.The fine structural changes characteristic of this disease are summarized and it is concluded that histochemical studies alone are insufficient to exclude the diagnosis of McArdle's myopathy.     

The Studies of the Attacks of Abnormal Eye Movement in a Case of Infantile Spasms

We observed the attacks of nystagmus in a case of infantile spasms and carried out overnight sleep polygraphy. The following findings were obtained:

• 1 Awake time was prolonged to 56% of TIB, while sleep time was markedly shortened to 44% of TIB. Also REM sleep time was reduced to 20% of SPT and deep slow sleep (stage N3) was absent.
• 2 Attacks of nystagmus were observed only during wakefulness. At first, fast wave bursts appeared in the right occipital area, and were followed by left-upward deviations of eyeballs, and then the attacks of counterclockwise right-downward rotatory nystagmus. Also the fast wave bursts were succeeded by spreading of fast waves to adjacent areas. At the same time, EMG exhibited elevated muscle action potentials of mentalis and biceps fernoris. During the attacks of nystagmus, there was alteration of respiratory movements.

In NREM sleep, both fast wave bursts and the attacks of nystagmus were not observed. In REM sleep, the fast wave bursts and eye movements were observed but the attacks of nystagmus did not appear. During the fast wave bursts, alteration of respiratory movements were observed. From the results of this study, it was presumed that the brain lesions of this case were extended with severe degree of damage in the great parts of brain containing Cerebral cortex and brain stem.     

Aggregated plasmalemmal vesicles and microvilli in human astrocytoma

Summary Plasmalemmal vesicles and microvilli or filopodia in human astrocytoma were examined with thin-section and freeze-fracture techniques. The plasmalemmal vesicles, although sparsely scattered in distribution, were often aggregated in a curvilinear, semicircular, or circular fashion, and the involved plasma membrane was often protruded externally like a mound.Microvilli or filopodia were cross-fractured when fracture travelled within the plasma membrane resulting in a fracture face interrupted by numerous holes of cytoplasms. The microvilli were distributed in a concentrated manner on the free suface of the cell and often closely oriented in a linear, curvilinear, or circular fashion. They varied in size, form, and length. When they were arisen from a common hillock of the plasma membrane, its fracture face was elongated, up to 0.8 in length. Fenestrae were occasionally visible in attenuated cytoplasm which surrounded peripheral vacuole in the cell.     

Effects of local injection of ex vivo expanded autologous tumor-specific T lymphocytes in cases with recurrent malignant gliomas.

PURPOSE: The aim of this report was to indicate both the advantages and disadvantages of local cell transfer therapy using ex vivo expanded autologous tumor-specific T lymphocytes (ATTLs) for recurrent cases of malignant gliomas. EXPERIMENTAL DESIGN: Subjects are 10 cases of malignant gliomas consisting of 7 cases of glioblastoma multiforme, 2 cases of anaplastic astrocytoma, and 1 case of anaplastic oligoastrocytoma. All cases were recurrences. ATTLs were induced by coculturing peripheral blood mononuclear cells with autologous tumor cells in medium containing interleukin-1, -2, -4, and -6 and administered into the local tumor site in total numbers of 3-247 x 10(7) cells. As end points, tumor response and survival time were analyzed observing clinical state. RESULTS: Five cases responded to this therapy (namely, one case showed complete remission, and four cases had a partial response). There were three cases of no change, and two cases of progressive disease. The overall tumor response rate was 50%. No complications were noticed, except for two cases of minor local hemorrhage and eight cases of temporary fever. Nine cases died of further tumor progression, and one case died of aspiration pneumonia, and the cause-specific survival analysis indicates that the median survival time was 5 months from the initial ATTL injection. CONCLUSIONS: The results suggest that local administration of ATTLs is effective in recurrent malignant gliomas in that it demonstrated a high benefit:risk ratio with minor side effects. Although its antitumor effect may be temporary in some advanced cases, it is highly possible that the tumor could be stabilized when conditions are optimal.     

Long-term survival after radical resection of advanced pancreatic cancer

A 65-yr-old man who underwent pancreaticoduodenectomy with portal vein resection for pancreatic cancer is alive 8 yr after surgery. Originally, computed tomography (CT) revealed an 8-cm tumor in the pancreatic head. The tumor had infiltrated the portal vein, but grew expansively, so there was neither biliary obstruction nor jaundice. Pancreaticoduodenectomy with resection of the portal vein was performed for pancreatic cancer. Many tumor-infiltrating lymphocytes were seen within cancer cell nests on routine histopathology. We performed immunostaining for CD8, and found that a large number of the lymphocytes were CD8⁺ T cells. The patient’s prognosis was considered poor because the tumor was large and had infiltrated the portal vein. We suspect that long-term survival may be related to the response of CD8⁺ T cells to the cancer.     

Radioresponse of Thymomas Verified with Histologic Response

Patterns of radiologic response of 10 thymomas treated by preoperative radiotherapy (RT) (18-20 Gy/2 weeks) were determined in conjunction with histologic response. Changes in tumor volume were evaluated with CT scans obtained 5 to 36 days before and 14 to 24 days after the initiation of RT and before surgery. The extent of tumor volume reduction (TR) varied widely (40-78%), while the mean daily volume decrement expressed as a percentage of the pre-RT tumor volume correlated significantly with the pre-RT tumor volume. Histologically, the tumors, all of which were resected 17 to 33 days after RT initiation, generally consisted of predominant fibrous tissues, rare necrotic foci, and few epithelial cells. The TR did not correlate with pre-RT tumor volume, observation period, histologic subtype, or quantity of remaining epithelial cells. The TR of thymomas does not predict RT impact on tumor cells but does reflect the quantity of inherent tumor stroma.