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PubMed1988

Nuclear roundness factor measurement for assessment of prognosis of patients with prostatic carcinoma. I. Testing of a digitization system.

Standard pathological grading systems for prostatic carcinoma based upon glandular architectural pattern or nuclear anaplasia have failed to predict the prognosis of individual patients. Quantitative morphometric analysis of nuclear shape has predicted the outcome of patients with prostatic carcinoma when evaluated by some but not all reported studies. Calculation of nuclear roundness factor by different investigators was complicated by equipment differences and lack of standardized methods for acquiring and reporting data. We have improved our system for nuclear contour digitization and determined its theoretical limitations by digitizing standardized objects. Measurement errors were independent of orientation or location of an object within a microscopic or digitizer tablet field, speed of digitization and introduction of a microscope extension tube and light emitting diode cursor. Perimeters and areas of circles and squares of actual or digitizer-projected diameter or sidelength greater than five mm. were measured with a reproducibility and accuracy of greater than or equal to 90%. When a microscopic circle of diameter similar to prostatic carcinoma nuclei was digitized at a magnification of 2580 X, perimeter and area measurements differed within or between observers by less than 5% and were more than 95% accurate. In order to calculate accurately and evaluate NRF for use in assessing the prognosis of patients with prostatic carcinoma investigators must precisely describe their digitization system, standardization method and observer reproducibility and accuracy when measuring circles that approximate the projected size of prostatic carcinoma nuclei.

Carcinoma↗
PubMed1988

Nuclear roundness factor measurement for assessment of prognosis of patients with prostatic carcinoma. II. Standardization of methodology for histologic sections.

A nuclear shape descriptor, nuclear roundness factor, predicted outcome in patients with prostatic carcinoma whereas standard pathological grading by Gleason's architectural pattern did not. The inability of others to duplicate those successes warranted a reevaluation of the technique for NRF measurement. We previously described our digitization system and measured the perimeter and area of a microscopic circle similar in size to prostatic carcinoma nuclei with a reproducibility and accuracy of greater than 95%. We have applied our improved system to nuclear contour digitization and standardized our method for NRF measurement. In order to calculate accurately the NRF for prostatic carcinoma, the histologic section must have been reviewed by a pathologist and 150 nuclei traced after random selection. NRF measurement reproducibility within and between observers exceeded 90%. This system for NRF measurement successfully predicted outcome in 13 of 15 patients with stages A2, B1, and B2 prostatic carcinoma. Our success with a carefully tested and improved system for NRF determination warrants further evaluation of NRF for assessment of prognosis of patients with prostatic carcinoma.

Carcinoma↗
PubMed1999

Altered surface and cyst epithelium of ovaries removed prophylactically from women with a family history of ovarian cancer.

Despite intensive investigation, the nature of epithelial ovarian cancer precursors remains controversial. Because women with a strong family history of ovarian cancer have a high probability of developing ovarian cancer themselves, ovaries removed prophylactically from such patients provide an opportunity to identify early neoplastic changes. Ovaries removed from 64 consecutive patients undergoing prophylactic oophorectomy and from 30 women with normal ovaries and no known family history of ovarian cancer were examined by light microscopy for a number of histopathologic features and by image cytometry for abnormalities of the cyst and surface epithelium. All analyses were performed without knowledge of the family history. Seven benign, but no tumors of low malignant potential or malignant epithelial tumors were found in the prophylactic oophorectomy group. There were more cortical inclusion cysts in the prophylactically removed than controls ovaries (P = .016), but no other architectural features differed between the two groups. No abnormalities were found in the surface or cyst epithelium in either group by light microscopy. In contrast, image analysis identified differences in the nuclei between the two groups, indicating that those from the surface epithelium of prophylactically removed ovaries were larger and contained more heterogeneously dense chromatin than those of controls, and that nuclei of the cyst epithelium had more irregular outlines. Ovarian epithelium from prophylactically removed ovaries exhibit abnormalities that are only identified by image analysis, and which might represent early preneoplastic changes. Such ovaries may be useful for identifying early molecular changes in ovarian cancer.

Adult↗
PubMed1982

Karyometric studies and quantitation of the DNA content in nerve and oligodendroglial cells after intraperitoneal administration of Vincristine.

Karyometric and cytophotometric investigations were conducted on nuclei of nerve cells of the Gyrus cinguli and on oligodendroglial nuclei of the corpus callosum following a 12-fold intraperitoneal injection of Vincristine into Wistar rats. The results of our investigations have shown a distinctly decreased content of DNA in neuronal nuclei of experimental rats along with a slightly increased content of DNA in glial cells. It is assumed that intraperitoneal administration of Vincristine does not inhibit the replication of DNA by oligodendroglial cells and that the observed reduction of DNA in neurocytes is the result of a disturbed turnover of DNA that is due to some damage of cytoplasmatic structures (rough endoplasmatic reticulum and microtubules) induced by the applied cytostatic compound.

Animals↗
PubMed1986

Histoenzymatic, karyometric, and DNA cytophotometric studies on rat neuroglia following administration of BCNU (carmustine).

BCNU is a nitrosourea derivative applied in anti-neoplastic therapy. As a result of conversion under in vivo-conditions, products of alkylating properties are formed which derrange DNA metabolism, and products of carbamylating activity which disturb protein metabolism. Studies on BCNU neurotoxicity were performed on 20 adult rats of Wistar strain which were given the compound intraperitoneally, in doses corresponding to those used for tumour treatment in humans. Material for estimating unfavorable effects of the drug on central nervous system involved brains, the sections of which were subjected to histoenzymatic reactions and stained according to FEULGEN for karyometric studies and DNA cytophotometry. Size and shape estimates for nuclei of the cells and their DNA content were obtained using Morphoquant automatic microscopic image analyzer (VEB Carl Zeiss, Jena) and compared to those of neuroglia of control animals, given no drug. Multiple intraperitoneal injections of BCNU induced distinct histoenzymatic, karyometric, and cytophotometric changes in oligodendroglia and astroglia. In oligodendroglia, lowered NsE and AcP activities and augmented TPPase activity were noted while in astroglia decreased activity of the former 2 enzymes was associated with an augmented ATPase activity. In karyometric studies, significant decrease in the size of astroglia and in DNA extinction was noted. No karyometric or cytophotometric alterations were noted in oligodendroglia nuclei. Results of the presented studies may indicate primary injury to vascular walls and secondary damage to neuroglia.

Acetylcholinesterase↗
PubMed1987

Blood vessel endothelia in rat brain following experimental administration of BCNU (carmustine): karyometric studies and cytophotometric studies on DNA.

Studies on the effect of BCNU (Carmustine), administered in 4 intraperitoneal injections of 7.5 mg each, on cell nuclei of blood vessel endothelia were performed on the parietal cortex and the thalamus of 20 adult rats of Wistar strain. Karyometric studies demonstrated increased circumference and cross-section area of cell nuclei in vascular endothelia following administration of the cytostatic drug. The nuclei acquired a more spheric shape and a decreased surface irregularity (decreased folding) of their cross-sections. Extinction of endothelial cell nuclei estimated following administration of BCNU showed also an increased content of DNA as well as a more compact and concentrated nuclear chromatin. The alterations noted in endothelial nuclei of thalamic blood vessels were more pronounced than those seen in the parietal cortex.

Animals↗
PubMed2002

Saw palmetto alters nuclear measurements reflecting DNA content in men with symptomatic BPH: evidence for a possible molecular mechanism.

OBJECTIVES: To examine the nuclear chromatin characteristics of epithelial cells, looking for an SPHB-mediated effect on nuclear DNA structure and organization. Saw palmetto herbal blend (SPHB) causes contraction of prostate epithelial cells and suppression of tissue dihydrotestosterone levels in men with symptomatic benign prostatic hyperplasia, but a fundamental mechanism remains unknown. METHODS: A 6-month randomized trial, comparing prostatic tissue of men treated with SPHB (n = 20) or placebo (n = 20), was performed. At baseline, the two groups were similar in age (65 versus 64 years), symptoms (International Prostate Symptom Score 18 versus 17), uroflow (maximal urinary flow rate 10 versus 11 mL/s), prostate volume (59 versus 58 cm(3)), prostate-specific antigen (4.2 versus 2.7 ng/mL), and percentage of epithelium (17% versus 16%). Prostatic tissue was obtained by sextant biopsy before and after treatment. Five-micron sections were Feulgen stained and quantitatively analyzed using the AutoCyte QUIC-DNA imaging system. Images were captured from 200 randomly selected epithelial cell nuclei, and 60 nuclear morphometric descriptors (NMDs) (eg, size, shape, DNA content, and textural features) were determined for each nucleus. Logistic regression analysis was used to assess the differences in the variances of the NMDs between the treated and untreated prostate epithelial cells. RESULTS: At baseline, the SPHB and placebo groups had similar NMD values. After 6 months of placebo, no significant change from baseline was found in the NMDs. However, after 6 months of SPHB, 25 of the 60 NMDs were significantly different compared with baseline, and a multivariate model for predicting treatment effect using 4 of the 25 was created (P <0.001). The multivariate model had an area under the receiver operating characteristic curve of 94% and an accuracy of 85%. CONCLUSIONS: Six months of SPHB treatment appears to alter the DNA chromatin structure and organization in prostate epithelial cells. Thus, a possible molecular basis for tissue changes and therapeutic effect of the compound is suggested.

Aged↗
PubMed1996

Quanticyt: karyometric analysis of bladder washing for patients with superficial bladder cancer.

OBJECTIVES: Quantitative cytology by image-analysis techniques enables objective interpretation of nuclear features in light microscopic images. QUANTICYT, a quantitative karyometric cytology system, was used in the follow-up of patients with superficial bladder cancer. METHODS: From 1992 to 1995, 4137 samples from 1412 patients were obtained. At 1-year follow-up after the initial bladder washing, a tumor recurrence rate of 21% was found. In this period, tumor progression to invasive disease occurred in 1.6% of patients. Scoring of tumor by the QUANTICYT system was based on two nuclear features: the 2c deviation index and the mean of a nuclear shape feature: MPASS. RESULTS: The method was found to be reproducible and superior to visual cytologic interpretation. QUANTICYT analysis of the bladder washings resulted in a score of low, intermediate, and high risk. In a multivariate analysis, highest grade of earlier tumor and QUANTICYT risk score were the best predictors of tumor recurrence and progression. For the easy application of QUANTICYT analysis in daily routine, a report form that included patient history and DNA histogram was developed. CONCLUSIONS: QUANTICYT karyometric analysis of bladder-wash material proved a useful, clinically applicable grading tool in the follow-up of patients with superficial bladder cancer, with sufficient power to be used in decision-making in the individual patient.

Administration, Intravesical↗
PubMed2000

Prognostic value of nuclear morphometry on needle biopsy from patients with prostate cancer: is volume-weighted mean nuclear volume superior to other morphometric parameters?

OBJECTIVES: To compare the prognostic value of stereologically estimated volume-weighted mean nuclear volume (MNV) with other nuclear morphometric parameters using pretreatment needle-biopsy specimens of prostate cancer. METHODS: The MNV, mean nuclear area, form factor, and coefficients of variation for nuclear area (VNA) and form factor were measured on pretreatment needle biopsy specimens from 66 patients with prostate cancer (clinical Stage B, n = 9; Stage C, n = 14; and Stage D, n = 43), all of whom underwent androgen deprivation therapy. The prognostic value of those morphometric parameters, as well as Gleason score and clinical stage, was examined in terms of cause-specific patient survival using univariate and multivariate analysis (Cox proportional hazard model). RESULTS: Univariate analysis of the nuclear morphometric parameters revealed that MNV, mean nuclear area, VNA, coefficient of variation for form factor, and clinical stage were significant prognostic factors for cause-specific patient survival. However, when the patients with Stage D disease were selectively analyzed for survival, only the VNA was a significant prognostic parameter. Furthermore, the multivariate analysis, including the morphometric parameters, clinical stage, and Gleason score revealed that only VNA and clinical stage were independent variables. CONCLUSIONS: The present comparative study could not demonstrate any prognostic superiority of MNV over other nuclear morphometric parameters in patients with prostate cancer.

Aged↗
PubMed2000

Presence of carcinoma in situ and high 2C-deviation index are the best predictors of invasive transitional cell carcinoma of the bladder in patients with high-risk Quanticyt.

OBJECTIVES: Karyometric analysis (Quanticyt) has proved of value as a cytologic marker for bladder cancer. This study was conducted to identify diagnostic and prognostic factors in a high-risk Quanticyt population to predict the prognosis of transitional cell carcinoma (TCC) of the bladder. METHODS: Quanticyt is a karyometric system for quantitative bladder wash cytologic findings based on two nuclear features: the 2c-deviation index (2cDI) and the mean of nuclear shape. Samples are scored as low, intermediate, or high risk. Before 1995, 109 patients with high-risk quantitative bladder wash cytologic findings were identified at our clinic. Four patients with previous invasive tumors were excluded. RESULTS: Histologically proven malignancy was found in 54 of 105 patients at first high-risk quantitative bladder wash cytologic findings. Invasive TCC was found in 16 patients, and another 10 patients had progression during a median follow-up of 3.7 years. In univariate analysis, the presence of carcinoma in situ (CIS), highest tumor grade, 2cDI, and highest tumor stage were significant predictors of progression. The presence of CIS proved to be the only predictor of progression in the multivariate analysis. A 2cDI of 2.00 c(2) or higher was a significant predictor of CIS, invasive TCC, and progression. At follow-up analysis after negative cystoscopy, 2cDI showed a tendency toward predicting progression. CONCLUSIONS: These data confirm earlier findings that CIS is an important marker of progression. 2cDI as assessed by quantitative cytology is a practical tool to predict CIS, invasive TCC, and subsequent progression. A 2cDI of 2. 00 c(2) can be used to further stratify high-risk quantitative bladder wash cytologic findings.

Adult↗
PubMed1984

Modern developments in histopathologic assessment of uveal melanomas.

Uveal melanoma is the most common primary intraocular neoplasm in adults. Those histopathologic features that distinguish uveal nevi from small melanomas, and those that distinguish highly malignant from less malignant lesions, have been the subject of controversy over the past decades. This controversy arises primarily from the subjective methods by which such histopathologic distinctions are made, and the resulting ambiguities may have misguided the clinician in his management of certain uveal lesions. With methods made possible by modern technology, pathologists can now assess the malignant potential of uveal melanomas by objective measurement of cytologic structures within the tumor.

Cell Nucleolus↗