Expression of Ki-67, cyclin D1 and apoptosis markers correlated with survival in prostate cancer patients treated by radical prostatectomy.

OBJECTIVE: The study was designed to analyse the prognostic value of proliferation markers Ki-67 and cyclin D1 and apoptosis in prostate cancer (PC) patients treated by radical prostatectomy. PATIENTS AND METHODS: Two hundred and eleven patients treated by radical prostatectomy for localised prostate cancer were clinically followed up for a mean of 7.3 years. The primary histopathological specimens were re-analysed to ensure uniform histoplthological grading and pT classification. A tissue microarray construction (TMA) was used in immunohistochemisty to assess the expression of Ki-67, cyclin D1 and the apoptosis marker Tag. The results were analysed with light microscopy and the findings were compared to standard histology, pT and clinical follow-up data. RESULTS: The co-expression of Ki-67 and cyclin Dl (p=0.05) was common. High fraction of Ki-67 positive cells and a high fraction of apoptotic cells were often present in same tumours (p=0.05). High apoptotic rate was related to positive surgical margin status (p=0.047). Low expression of Ki-67 was related to a low Gleason score (p<0.001), an absence of either capsule penetration (p = 0.029) or perineural invasion (p=0.004). High expression of cyclin Dl was related to perineural growth (p=0.039). Prostate specific antigen (PSA) recurrence-free survival (RFS) was predicted by Gleason grade (p<0.001) and capsule invasion (p=0.006). High expression of Ki-67 (p=0.03), as well as high apoptotic rate (p=0.04) were related to a high risk of cancer death. In multivariate analysis the seminal vesicle invasion was the only independent predictor of cancer death (p = 0.01). CONCLUSION: The expression of Ki-67, cyclin D1 and a high apoptotic rate are related to a malignant phenotype in prostate cancer, but their prognostic value is inferior to standard histological prognostic factors.

Reduced alpha- and beta-catenin expression predicts shortened survival in local prostate cancer.

UNLABELLED: The aim of this study was to determine the prognostic value of alpha- and beta-catenin expressions in local prostate cancer (PC). MATERIALS AND METHODS: One hundred and eighty-one PC patients treated with radical prostatectomy were followed-up for a mean of 7.3 years. The alpha- and beta-catenin expression were analysed by immunohistochemistry TMT (tissue microarray technique) and light microscopy. RESULTS: Strong a-catenin expression was related to low Gleason grade (p < 0.001), cancer-free seminal vesicles (p = 0.04) and low preoperative PSA (p = 0.02). Strong beta-catenin expression was related to low Gleason grade (p < 0.001) and cancer-free seminal vesicle status (p = 0.03). Absence of nuclear beta-catenin expression was related to local disease (pT1-T2) (p = 0.05). alpha-catenin (p = 0.06), beta-catenin (p = 0.05), Gleason grade (p = 0.03) and capsular invasion (p = 0.01) were related to PSA recurrence in patients who reached PSA zero postoperatively. PSA recurrence-free survival (RFS) was significantly related to Gleason grade (p < 0.001), capsule invasion (p = 0.01), perineural growth (p = 0.05) and preoperative PSA (p = 0.05). In Cox's analysis, independent predictors of PSA RFS were Gleason grade (p < 0.001) and capsular invasion (p = 0.006). Low expressions of alpha- (p = 0.06) and beta-catenin (p = 0.05) were related to shortened PSA RFS. Survival was related to low alpha- (p = 0.011) and beta-catenin (p = 0.016) expressions. Independent predictors of shortened survival were seminal vesicle invasion (p = 0.016) and low alpha-catenin expression (p = 0.049). CONCLUSION: Reduced alpha- or beta-catenin expressions are related to malignant phenotype in local prostate cancer and predict PSA failure as well as shortened survival.

Castleman's disease of the leptomeninges--immunohistochemical findings in 2 cases.

OBJECTIVE: Castleman's disease is an uncommon benign lymphoproliferative disorder that arises in lymph nodes. Few cases of Castleman's disease affecting the central nervous system have been described. CASE HISTORY: We report 2 new cases of Castleman's disease confined solely to the leptomeninges. The patients were referred to neurosurgery with presumptive clinical diagnosis of meningiomas. Histological investigation of the operative specimens taken from the abnormal leptomeninges revealed nodular lymphoid areas with multiple germinal centers surrounded by concentrically layered proliferations of small lymphocytes. Histologically, these 2 cases fulfilled the classification criteria for the mixed and for the hyaline-vascular type of Castleman's disease. The immunohistochemical analysis revealed a polyclonal B cell proliferation in the lesions with perifollicular T cell proliferation with the T helper cell predominance. CONCLUSIONS: The authors conclude that Castleman's disease involving the leptomeninges have a similar immunological pattern reported for the disease in extracranial locations and that, though being rare, Castleman's disease should be considered as a differential diagnosis when dealing with mass lesions of leptomeninges.

Strong Stromal Hyaluronan Expression Is Associated with PSA Recurrence in Local Prostate Cancer.

OBJECTIVE: HA (hyaluronan) is involved in cell migration, differentiation and cell proliferation, which all are essential to tumour growth. In addition, the cell surface receptor of HA, CD44, is important in cancer cell adhesion, cell migration and tumour neovascularisation. We studied the expression of HA and CD44 and their relationship with other prognostic factors and prostate-specific antigen (PSA) recurrence in local prostate cancer (PC). MATERIALS AND METHODS: 77 PC patients treated with radical prostatectomy were followed-up for a mean of 4 years. HA was detected by using a HA specific probe and CD44 expression was analysed by conventional immunohistochemistry. RESULTS: All specimens expressed HA in tumour stroma and 78% (60/77) of the tumours showed strong stromal expression of HA. The fraction of positively stained specimens for CD44 was 66% (51/77). The strong stromal HA expression was related to perineural infiltration (p = 0.001) and capsule invasion (p = 0.05). No correlation was demonstrated between the stromal HA expression and CD44 expression, preoperative PSA, clinical or pathological T classification, pN status, Gleason grade, seminal vesicle invasion or surgical margin invasion. Reduced CD44 expression was related only to preoperative PSA level (p = 0.008). The PSA recurrence was predicted by strong stromal HA expression, pT classification, seminal vesicle invasion, capsule invasion and surgical margin invasion (p

Bone marrow micrometastases in patients with stage I-II localised prostate cancer.

Prostate cancer commonly metastasises to the bones. Detection of bone marrow micrometastases (BMM) may give important information that helps define treatment strategies. This study was undertaken to analyse BMM in early prostate cancer patients and to determine the accuracy of immunohistochemical (IHC) and morphological methods in detecting cancerous cells. Preoperative core bone marrow biopsy (BMB) was performed in 103 patients with T1-2, N0, M0 prostate cancer after neoadjuvant androgen blockade. BMB were examined by IHC using monoclonal antibodies for cytokeratins (CK) (18, 19, PAN) and by cytomorphology of IHC-positive cells. In 103 patients, BMM were detected in 2 cases (2%) and an additional 3 cases (3%) were classified as suspicious. IHC alone revealed positive cells in 19 patients (18%). Cytomorphology disclosed IHC false-positive staining of some apparently normal bone marrow elements such as plasmocytes. The study shows a rather low rate of BMM in early prostate cancer. It also stresses the importance of cytomorphology as an adjunct to IHC as IHC alone may not be sufficient and appropriate for BMM detection.

Prognostic value of CD44 standard, variant isoforms 3 and 6 and -catenin expression in local prostate cancer treated by radical prostatectomy.

OBJECTIVE: The clinical and histological data of prostate cancer patients were compared with the expression of CD44 standard (CD44s), variant isoforms CD44v3, CD44v6 and alpha-catenin. The prognostic value of these adhesion molecules was also analysed. PATIENTS AND METHODS: We analysed the clinical and histological data of 87 prostate cancer patients treated by radical prostatectomy in two Finnish hospitals. The mean (SD) age of the patients at diagnosis was 64 years (6) and the mean follow-up was 3 years (8). Immunohistochemistry was used to detect the expression of CD44s and its v3 (CD44v3) and v6 (CD44v6) isoforms and alpha-catenin. RESULTS: The mean (SD) fractions of positively stained cancer cells were 38 (38), 10 (22), 56 (41) and 93% (17) for CD44s, CD44v3, CD44v6 and alpha-catenin, respectively. Low fractions of CD44s- and CD44v6-positive cancer cells were related to high preoperative prostate-specific antigen (PSA) levels (p<0.05 for both). Low fraction of CD44s positive cancer cells was linked with presence of seminal vesicle invasion (p = 0.07), surgical margin positivity (p = 0.09), high Gleason score (p = 0.04) and high mitotic index (p = 0. 02). Low fraction of CD44v3-positive cancer cells was related to positive surgical margins (p = 0.05), high Gleason score (p = 0.04), presence of perineural infiltration (p = 0.02) and absence of tumour-infiltrating lymphocytes (p = 0.02). Low fraction of CD44v6-positive cancer cells was related to high pT classification (p = 0.07), capsule invasion (p = 0.03), positive surgical margins (p = 0.05), high Gleason score (p = 0.008), perineural infiltration (p = 0.0001) and high mitotic index (p = 0.001). alpha-Catenin expression was not related to any of the clinicopathological variables included in this study. Gleason score (p = 0.001), pT classification (p = 0.007), perineural infiltration (p = 0.01) and the fraction of CD44v3-positive cancer cells (p = 0.04) were predictors of PSA failure in univariate analysis. pT category (p = 0. 012), Gleason score (p = 0.02) and expression of CD44v3 (p = 0.0003) were independent predictors of PSA failure. CONCLUSIONS: The expression of CD44s, CD44v3 and CD44v6 is related to tumour differentiation. The expression of CD44v3 independently predicts PSA failure in addition to Gleason score and pT category during a short-term follow-up.

The prognostic value of inducible nitric oxide synthase in local prostate cancer.

OBJECTIVE: To compare the clinical and histological data from patients with prostate cancer with the results of the immunohistochemical analysis of inducible nitric oxide synthase (iNOS), and thus determine the prognostic value of iNOS. PATIENTS AND METHODS: The study included 82 patients (mean age 64.6 years, SD 6.1) with local prostate cancer treated by radical prostatectomy in two Finnish hospitals. Their mean (SD) follow-up was 3.3 (2.2) years. An immunohistochemical method was used to detect the expression of iNOS in these specimens, and the expression graded according to staining intensity as none, weak or strong. RESULTS: There was weak or strong expression of iNOS in 25 (31%) and 56 (68%) of the patients, respectively, and one specimen was negative for iNOS. Strong expression of iNOS was related to high a preoperative prostate specific antigen (PSA) level (P = 0.006) and high pT classification (P < 0.001), but not to nodal status, grade, seminal vesicle or capsular invasion, surgical margin status, perineural infiltration, tumour infiltrating lymphocytes or proliferation rate of cancer cells. A PSA failure was detected in 29 patients but was not predicted by iNOS expression. A Cox multivariate analysis showed that surgical margin positivity, seminal vesicle involvement and number of tumour infiltrating lymphocytes predicted the PSA failure. CONCLUSION: A high expression of iNOS was related to a high pT classification and the preoperative PSA level but not to other established prognostic factors; iNOS expression was not a predictor of PSA failure in patients with local prostate cancer.

Quantitative analysis of tryptase and chymase containing mast cells in benign and malignant breast lesions.

The aim of our work was to study the number and distribution of tryptase- and chymase-containing mast cells in benign and malignant breast lesions. Tryptase positivity reflects the total number of mast cells, whereas chymase is not present in all mast cells. Active forms of tryptase and chymase were demonstrated enzymo-histochemically in 30 benign and 98 malignant fresh frozen breast lesions, which were graded and analysed morphometrically and statistically. The exclusive presence of tryptase and chymase in mast cells was confirmed in 5 cases by a sequential double-staining method. In benign lesions, the number of mast cells exhibiting tryptase activity was similar to that of chymase-active mast cells. Malignant tumours, however, had 2 to 3 times more tryptase-containing than chymase-containing mast cells, while the number of mast cells with tryptase activity was significantly higher (p < 0.02) than in benign lesions. In malignant lesions, tryptase-containing mast cells were concentrated at the tumour edge, i.e., the "invasion zone," whereas chymase-containing mast cells were not increased in this area.

Squamous cell carcinoma of the conjunctiva. Failure to demonstrate HPV DNA by in situ hybridization and polymerase chain reaction.

Squamous cell carcinoma of the conjunctiva is a distinct rarity, often arising at the corneoscleral limbus and initially resembling pterygium or chronic keratoconjunctivitis. In this paper we report 4 patients with conjunctival squamous cell carcinoma/carcinoma in situ, which comprise all the cases found in the files of Kuopio University Hospital during 1959-1991. The clinical appearance, diagnosis and treatment of the lesions are described. All biopsies were studied for the presence of Human papillomavirus (HPV) DNA (recently demonstrated in conjunctival squamous cell papillomas, precancer lesions and carcinomas) by using in situ DNA hybridization (ISH) and polymerase chain reaction (PCR). Both techniques failed to demonstrate the DNA of any of the following HPV types: HPV 6, 11, 16 and 18 in any of the lesions. The results are discussed in the light of the recently proposed HPV etiology of these lesions.

CO2 gas perfusion: improved efficiency and safety with sapphire-probe laser ablation of human artery.

CO2 gas has been proposed as a new perfusion medium for laser angioplasty. To compare CO2 gas with conventional saline perfusion, 146 fresh specimens of normal and atheromatous human artery were irradiated with a neodymium: yttrium-aluminum-garnet laser with a sapphire probe in flowing whole blood in an experimental circulation-occlusion model. The dimensions of the ablation crater and the extent of the surrounding tissue damage were measured microscopically. Significantly better ablation of atheromatous plaque was achieved with CO2 perfusion than with saline perfusion: mean ablation areas were 5.0 mm2 versus 2.8 mm2, respectively (P = .001, Student t test). In contrast, the ablation areas on normal vessel wall were identical (mean, 3.4 mm2) with the two perfusion media. Moreover, CO2 gas functioned as a negative contrast agent and facilitated direct monitoring of the laser recanalization procedure. On an experimental basis, CO2 gas perfusion seems to improve the efficiency and safety of laser ablation in human arteries.

Carbon dioxide gas as a perfusion medium for the sapphire probe in laser ablation of human atheromatous plaques: comparison study with saline.

The effectiveness of CO2 gas as a perfusion medium was compared to that of saline in laser ablation of human atheromatous plaque. In an experimental circulation-occlusion model using flowing whole blood, human cadaveric arterial samples were irradiated by a sapphire probe with the Nd-YAG laser. The following experiments were performed: 1) lasing without perfusion, 2) lasing with saline perfusion of the probe, and 3) lasing with CO2 perfusion. Different perfusion flow rates of saline and CO2 were used. Results showed that the mean ablation area was 1.6-fold larger with CO2 than with saline perfusion (P less than 0.05, Student's t test). The mean lateral injury at the site adjacent to the ablation crater and at the area directly facing the probe was not significantly different with either perfusion medium. The larger ablation area with CO2 was probably due to the fact that CO2 is a good insulator for maintaining a higher probe temperature and keeps the probe free of blood debris. In conclusion, our results show that CO2 perfusion facilitates more effective laser ablation of atheromatous plaque than saline perfusion by the sapphire probe with the continuous wave Nd-YAG laser.