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S Pervez

Publications and source records attributed to S Pervez.

At least 19 recordsLinked to original sources

DNA ploidy and S-phase fraction analyses of hyperplastic, atypical and cancerous endometrium using flow cytometry from paraffin-embedded tissues.

Atypical hyperplasia of the endometrium is an entity that needs to be clearly distinguished from other florid hyperplastic states on the one hand and from well-differentiated adenocarcinomas on the other. This may at times be difficult on pure morphological grounds. In this study, DNA ploidy and S-phase fraction of hyperplastic, atypical and cancerous endometrium were evaluated using flow cytometry from paraffin-embedded tissues. In total, 72 cases (24 hyperplastic, 24 atypical and 24 adenocarcinomas) were selected. All hyperplastic endometria showed a diploid stemline, while 2/24 atypical hyperplasias showed aneuploid (Near-diploid) peaks. Both of these cases were severely atypical and one of these, on hysterectomy, showed early invasive carcinoma. There was no significant difference in mean S-phase fractions of hyperplastic vs. atypical endometria. DNA aneuploidy was significantly more common with much higher S-phase fractions in poorly and moderately differentiated carcinomas than in well-differentiated ones. It was concluded that aneuploid (near-diploid) peaks, if ever present in atypical hyperplasias, may indicate an aggressive disease/neoplastic transformation.

Adenocarcinoma↗

Epidermal growth factor receptor (EGFR) as a prognostic marker: an immunohistochemical study on 315 consecutive breast carcinoma patients.

OBJECTIVE: To assess the independent and interdependent prognostic value of epidermal growth factor receptor (EGFR) in carcinoma of breast in female population. The Type 1 family of growth factor receptors includes epidermal growth factor receptor (EGFR also known as EGFR1). METHODS: The expression of EGFR protein was analysed immunohistochemically on 315 tumour specimens of infiltrating ductal carcinoma of breast. These patients also had axillary lymph nodes sampling. RESULTS: Overexpression and/or amplification of EGFR was observed in 70 (22.00%) tumours. Eleven (16%) were grade I, 43 (61%) grade II and 16 (23%) grade III tumours. Axillary lymph node metastasis had significant correlation with intensified positivity of EGFR (p < 0.05). Significant number of EGFR positive patients developed local recurrence and distant metastases to brain, liver and bone (p < 0.05). EGFR positivity showed significant correlation with the disease free and overall survival (p < 0.05). At a median follow-up of 48 (4 years) months in EGFR positive patients, the overall survival was 3.39 years and disease free survival was 2.86 years. EGFR negative tumour patients showed a better survival. In this group the overall survival was 4.62 years and the disease free survival was 4 years. CONCLUSION: EGFR analysis can be a useful indicator for the selection of patients who are at the high risk, for hormonal therapy decisions and can be useful as a target for new treatment modalities.

Adult↗

Clinical, pathological and molecular factors predicting axillary node involvement in primary breast cancer in Pakistani women.

BACKGROUND: Axillary lymph node involvement in primary breast cancer is one of its most important prognostic features. Thus any factors that may predict axillary lymph node involvement in this setting could be potentially helpful in treatment planning and other interventions. OBJECTIVE: The objective of this study was to evaluate clinical, pathological and immuno-histochemical markers in univariate and multivariate analysis, which may be helpful predictors of axillary lymph node involvement in breast cancer. METHOD: A retrospective analysis of 555 cases. Of these 58% had axillary nodal positivity and 42% were negative. CONCLUSION: Factors of no significance included patient's age, height, weight, age of first pregnancy, parity, marital status, menopausal status, family history of breast cancer, side of tumor. In univariate analysis the age of menarche, duration of symptoms, tumor size, site in outer quadrant, S phase and skin and nipple involvement all predicted axillary nodal involvement. The length of breast-feeding, increased intraductal component and increased PCNA were inversely proportional to nodal involvement. In multiple regression analysis however only size of the tumor, involvement of the skin and nipple and disease in the outer quadrant of breast were the factors, which assumed significance.

Axilla↗

Cancer patterns in Karachi division (1998-1999).

OBJECTIVE: A minimal cancer incidence data for Karachi, the largest city of Pakistan, is being presented here, for the years 1998-1999. The city has a population of 9,802,134; males 5,261,712 (52.6%) and females 4,540,422 (47.4%); census 1998. METHODOLOGY: A predominantly mixed (passive and active) registration system has evolved in Karachi, the data sources being the hospitals within the Karachi Division. The reported/retrieved cancer data sets at the Karachi Cancer Registry are checked, coded, computerised in an analytical format and analysed. RESULTS: The incident cancer cases registered in Karachi, during the 2-year period, 1st January 1998 to 31st December 1999 were analysed. The age-standardised incidence rate (ASR) of cancer, all sites was 132.4/100,000 for the males. Cancer of the lung 10.8%; ASR 17.3 was the most frequently recorded malignancy, followed by oral cavity 10.5%; ASR 13.2 and larynx 5.0%; ASR 7.4. The age-standardised incidence rate (ASR) of cancer, all sites was 133.0/100,000 in the females. Cancer of the breast, 32.0%; ASR 40.7 was the most frequently recorded malignancy, followed by oral cavity 8.1%; ASR 11.7 and gall bladder 3.6%; ASR 5.5. CONCLUSION: The present data has been calculated with an estimated 15-20% probable under ascertainment. Tobacco-associated cancers in Karachi were responsible for 38.3% of the tumours diagnosed amongst the males. Two principal cancers, breast and oral cavity were responsible for 40.1% of the cancers in females. A rare finding was the high incidence of gall bladder cancer in the females. At present it is difficult to determine whether this indicates a genuine high risk or a selection bias. A continuous process of cancer registration to study the trends in the incidence and an adequate cancer control program are possible and essential for Pakistan and can be based on the pattern being practiced in Karachi.

Breast Neoplasms↗

Transitional cell carcinomas of the urinary bladder. A histopathological study.

OBJECTIVE: To determine the histological grading and muscle invasion in Transitional Cell Carcinomas of the Urinary Bladder; and to evaluate whether any correlation exists between tumour grade and muscle invasion. METHOD: A Retrospective study of all consecutive cases of Transitional Cell Carcinomas of the Urinary Bladder diagnosed at Aga Khan University Hospital between 1st Jan 1997 and 31st Dec 2000. RESULTS: This study included 495 cases of Transitional Cell Carcinoma of the Urinary Bladder. M: F ratio was 4:1. Ages of patients ranged from 30 years to 87 years. Mean age in males was 59.1 years and in females 58.8 years. Forty four percent cases were Grade II, and 29.5% Grade III. None of the Grade I lesions were invasive, 10% Grade II tumours, 61.41% of Grade III and all Grade IV tumours were invasive. CONCLUSION: There is a definite correlation between advancing tumour grade and muscle invasion.

Adult↗

Folinic acid protects against suppression of growth by methotrexate in mice.

The objective of this study was to investigate whether folinic acid supplementation would protect young mice against suppression of growth by methotrexate (MTX). Four equal groups of Balb/c young male mice (5 animals in each group; mean+/-SD body weight 9.64+/-0.85 g, in their rapid growth phase) were subjected to the following drug treatment: One group was given MTX (3.5 mg/kg body weight) intraperitoneally on every 2nd day, another received folinic acid (7.0 mg/kg body weight) intraperitoneally every 2nd day. The third group was given both of these drugs (MTX on every 2nd day and folinic acid 8 h post-MTX injection). The fourth group was injected with physiological saline every other day to serve as a control group. Total body weight, food and water consumption by animals in each group were monitored every second day for a period of 3 weeks. After this period mice were sacrificed and liver, spleen and kidneys were excised, weighed and analyzed for MTX and dihydrofolate reductase activity. A small segment of the proximal part of small intestine and small pieces of liver and kidney were also removed to study morphological changes. Compared to the groups, which received folinic acid alone, folinic acid plus MTX or physiological saline, mean increase in body weight (6.8+/-0.8 g) of mice over a period of 3 weeks was minimal in the group receiving MTX alone (one-way ANOVA p=0.0001). The mean weights of liver and kidney in this group receiving MTX alone were also found to be significantly less than the mean weights of these organs in the 3 groups (p<0.001). The negative effect on growth of animals appears not only due to malabsorption but inhibition of pathway of de novo DNA synthesis may also be involved. This is supported by loss of villous pattern in small intestine of mice treated with MTX alone and increased accumulation of free MTX and decreased dihydrofolate reductase in the liver of the group receiving MTX alone as compared with the group receiving MTX plus folinic acid. The data indicate that the administration of folinic acid protects mice against suppression of growth by MTX. On the basis of these observations it can be deduced that patients suffering from juvenile rheumatoid arthritis or acute lymphoblastic leukaemia receiving MTX over a long period of time might be at a risk of experiencing short-term suppression of growth, however they could benefit from supplementation with folinic acid.

Animals↗

Significance of immunohistochemical c-ErbB-2 product localisation pattern for prognosis in human breast cancer.

Breast cancer is an increasingly important cause of illness and death among women. In recent years several novel prognostic determinants of breast cancer have been identified, including c-ErbB-2. In this study, expression of c-ErbB-2 in breast carcinoma was correlated with axillary lymph node metastases and disease outcome. The expression of c-ErbB-2 oncoprotein was analysed in 315 tumor specimens of infiltrating ductal carcinoma of breast. They were categorized according to the modified Bloom and Richardson criteria into three histological grades. These patients also had axillary lymph nodes sampling. The expression of c-ErbB-2 oncoprotein was analysed immunohistochemically. Over expression of c-ErbB-2 were observed in 39.36% tumors. Axillary lymph node metastasis had significant correlation with intensified positivity of c-ErbB-2. C-ErbB-2 positive patients did show resistance to chemotherapy when compared for recurrence and distant metastases following surgery (p< 0.05). At a median follow-up of 48 months in c-ErbB-2 positive patients, the overall survival was 3.0 years and disease free survival was 2.5 years. c-ErbB-2 negative tumor patients showed a far better survival. In this group the overall survival was 4.44 years and the disease free survival was 3.78 years. These findings reinforce the view that c-ErbB-2 immunohistochemical detection is of help in detecting a subgroup of breast carcinoma patients who are at high risk. This may also be of particular relevance in decisions regarding adjuvant chemotherapy to these patients.

Breast Neoplasms↗

DNA ploidy analyses in 218 consecutive Pakistani breast cancer patients: does it add anything?

An analysis was made to evaluate the significance of DNA ploidy in the biology and prognosis of breast carcinoma. This was done by estimating the correlation of DNA ploidy with other established prognostic markers of breast cancer, namely tumor size, tumor grade, lymph node metastasis and S-phase fraction. From 1995 up to year 2000 ploidy analysis was performed on 218 consecutive cases of infiltrating breast carcinoma by flow cytometry using formalin fixed paraffin embedded material. From the laboratory record, data regarding other pathological variables was retrieved. No correlation could be found between DNA ploidy and tumor grade, nor could there be found a correlation with tumor size. For lymph node metastasis there was a significant difference between the proportion of aneuploids and diploids having metastasis in more than 4 lymph nodes. However, no significant difference was found in axillary lymph node positive and negative groups when number of positive lymph nodes was not taken into account. The mean value of S-phase fraction for the aneuploids and the diploids was also insignificantly different. In conclusion DNA ploidy alone did not add much to predict tumor behaviour in terms of known pathologic variables.

Adult↗

Technetium-99m direct radiolabeling of lanreotide: a somatostatin analog.

Lanreotide, a synthetic octapeptide analog of a native hormone somatostatin, was labeled with a commonly available, inexpensive radionuclide 99mTc. Labeling was accomplished by reduction of the cysteine bridge, which provided sulfhydryl groups for chelation with 99mTc. Stannous chloride was used as reducing agent, while tartrate acted as transchelating agent. Lanreotide (100 microg), stannous chloride dihydrate (100 microg) and tartaric acid (64 microg) were dissolved in acetate/acetic acid buffer (pH 2.8). After overnight (approximately 18 h) incubation, approximately 444 MBq (12 mCi) 99mTc was added and kept in boiling water for 30 min. More than 97% labeling efficiency was confirmed by RP-HPLC, ITLC-SG and C18 cartridge analysis. Radiolabeling results in one major peak when analyzed by reverse-phase HPLC. The stability of the 99mTc-peptide bond was evaluated by cysteine challenge studies.

Chromatography, High Pressure Liquid↗

Evaluation and reinforcement of the correlation of S-phase fraction with nodal metastases, tumor grade and tumor size in breast carcinoma patients in Pakistan.

The aim of this study was to evaluate the S-phase fraction (SPF) of tumors in breast cancer patients in Pakistan. Its association with the traditional morphological prognostic markers, i.e., axillary lymph node metastasis, tumor size and grade, was also studied. Flow cytometry was used to estimate SPF on breast cancer tissues from 166 patients reported at the Aga Khan University Hospital between the years 1997 and 2000. Univariate analysis was done to find any association between SPF and the aforesaid variables. For the ease of analysis, the cases were subdivided into two categories depending on the SPF value, i.e., <10% (low-risk group) and > or = 10% (high-risk group). The mean and median SPF values were 21.45% and 20.035%, respectively, with a range of 3.26% to 54.30%. Twenty-six (15.66%) of the cases had SPF <10%, 57 (34.34%) had SPF from 10%-20%, and 83 (50%) had SPF >20%. A significant correlation between SPF and nodal metastasis was observed (p = 0.0111), but not between SPF and the number of lymph nodes involved when metastatic cases were subdivided into <4 lymph node-positive cases and > or =4 lymph node-positive cases. Significant correlations were also found between SPF and tumor grade (p = 0.0244), as well as between SPF and tumor size (p = 0.048). In conclusion, DNA flow cytometric analysis of SPF carried out in our laboratory could reasonably predict the chances of lymph node metastasis, tumor grade and size in breast cancer patients, thus proving to be an important prognostic marker in the Pakistani setting. This requires further investigations regarding the survival of patients so as to evaluate its capacity of predicting the outcome of Pakistani patients.

Adenocarcinoma↗

Immunohistochemical cathepsin-D expression in breast cancer: correlation with established pathological parameters and survival.

Breast cancer is an increasingly important cause of illness and death among women. In recent years, several novel prognostic determinants of breast cancer have been identified, including Cathepsin-D (CD) protein. CD protein expression was analyzed immunohistochemically (IHC) in tumor specimens (315 patients) of infiltrating ductal breast carcinoma. These patients also had axillary lymph node sampling. Overexpression of CD was observed in 39% of the tumors. IHC results were compared with the histological grade. Seventy nine percent (n = 95; 79%) tumor positivity was seen in grade II tumors, followed by grade I (n = 13; 11%) and grade III tumors (n = 12; 10%). Axillary lymph node metastasis had no significant correlation with CD positivity (p > 0.05). Bone metastases were significantly correlated with CD positivity (p < 0.05). CD positivity showed no significant correlation with disease-free and overall survival (p > 0.05). At a median follow-up of 48 (4 years) months in CD-positive patients, overall survival was 3.17 years, and disease-free survival 2.67 years. The overall survival of CD-negative tumor patients was 3.50 years, and disease-free survival was 2.93 years. We conclude that in comparison with cytosol-based quantitative studies, CD expression is not a good prognostic marker when, as in all ICH studies, only the expression in the tumor is considered.

Adult↗

Flow cytometric analysis of childhood leukemias.

OBJECTIVE: To collect demographic data for childhood (less than 15 years) leukemias in Karachi, describe the accuracy of the cell surface markers routinely used in the flow cytometric analysis of leukemic cells and arrive at an ideal panel of antibodies for analyzing leukemic samples. MATERIALS AND METHODS: Data from 62 consecutive cases of childhood leukemias referred to the Department of Pathology, Aga Khan University Hospital, (AKUH) between January 1995 and December 1998 was analyzed using Epi Info Version 6. Flow cytometry on all samples was performed using standard protocols. RESULTS: The mean age of patients was 8.2 years and 49 (79%) were males. Fifty (81%) had acute lymphoblastic leukemias of which 50% were CD10 positive and 24% CD10 negative Pre-B cell leukemias. Among all Pre B cell All 98% were positive for CD19, 96% for CD22, 89% for HLA-DR and 67% for CD10. Of the 10 AML cases, 100% were positive for CD33, 90% for CD13, 80% for CD19 and 70% for HLA-DR. CONCLUSION: The mean age in this study population was significantly higher and percentage of CD10 positive Pre-B All is lower than that in the West. Both these factors might be responsible for the poorer prognosis of these patients. It is not possible to specify a minimum or maximum panel of antibodies that should be used for phenotyping all cases of childhood leukemias. A certain degree or redundancy is essential in any panel of antibodies used for flow cytometry of leukemias.

Acute Disease↗

Histological pattern of central nervous system neoplasms.

OBJECTIVE: To see in a large series of patients the histological pattern of CNS neoplasms and to provide a comprehensive data about the frequency of CNS neoplasms in Pakistani patients and to give a clearer idea about their prevalence. METHOD: Retrospective study of all consecutive cases of CNS neoplasms diagnosed at The Aga Khan University Hospital (AKUH) between 1st January, 1994 and 31st December, 1999. SETTING: The section of Histopathology, AKUH, Karachi. OBSERVATION: Our series included a large number of cases i.e., 1110. There are very few local studies on CNS tumours and none so large. Our data was correlated with published Western and Pakistani data. Glial tumours were the commonest primary CNS neoplasms followed by meningiomas. Among glial tumours, astrocytomas comprised the largest group and the majority were high grade (III and IV) astrocytomas. Percentages of anaplastic oligodendrogliomas and ependymomas were also significant. Male to female ratio was 1.6:1. However, meningiomas were more common in females. Almost half of the CNS tumours in patients 15 years or younger were in the posterior cranial fossa. Metastatic tumours were much lower as compared to the West. CONCLUSION: Except for the high percentages of anaplastic oligodendrogliomas and ependymomas and the low percentage of metastatic tumours, most of our findings roughly correspond with the published data.

Adolescent↗

Morphological pattern of salivary gland tumours.

OBJECTIVE: To delineate the spectrum of salivary gland tumors in our setup. SETTING: The Aga Khan University Medical Centre, Karachi. METHOD: Tumors were analysed considering histological type, age and sex of the patients and anatomic location. The diagnosis of individual tumours was based on the 1991 World Health Organisation Classification. RESULTS: During the span of eight years (1991-1998), 379 cases of salivary gland tumours were diagnosed. Of these, 205 (65.7%) were male and 174 (34.3%) were female. The median age at the time of diagnosis was 35 years. The median age for patients with malignant lesions (44 years) was 12 years older than those with benign tumours (34 years). Overall, malignant tumours were seen more frequently in males, however benign tumours were distributed equally between the two sexes. The most common site was parotid gland (82.85%). Only five cases of minor salivary gland tumours were seen. The most frequently diagnosed benign salivary gland neoplasm was pleomorphic adenoma (84.5%), followed by Warthin's tumours (6.18%), Mucoepidermoid carcinoma was the most commonly encountered malignant lesion (56.9%), followed by adenoid cystic carcinoma (19.6%). CONCLUSION: Plemorphic adenoma was the most common benign salivary gland tumour and mucoepidermoid carcinoma was the most frequent malignant neoplasm. Parotid gland was the most common site of origin in both benign and malignant tumours. The overall relative frequency of salivary gland tumours in this series correlates with that reported in the international literature.

Adenoma, Pleomorphic↗

Relationship of p53 expression with clinicopathological variables and disease outcome: a prospective study on 315 consecutive breast carcinoma patients.

Breast cancer is an increasingly important cause of illness and death among women. In recent years several novel prognostic determinants of breast cancer have been identified which includes p53. Alterations of p53 are one of the most common abnormalities detected in primary breast cancer. In this study alteration of p53 in primary carcinoma breast was correlated with other pathological variables and disease outcome. In this prospective study the expression of p53 oncoprotein was analyzed immunohistochemically on 315 patient's tumour specimens of infiltrating ductal carcinoma of breast from 1992 to 1997. These patients also had axillary lymph nodes sampling. Both univariate and multivariate statistical analysis was performed to analyze results including disease outcome. Overexpression of p53 was observed in 55.23% tumours. Axillary lymph node metastasis had significant correlation with positivity of p53 (p<0.05). A significant number of p53 patients developed local recurrence and distant metastases to brain, liver, lung and bone (p< 0.05). At a median follow-up of 48 months (4 years) in p53 positive patients, the median overall survival (OS) was 3.0 years and disease free survival (DFS) was 2.5 years. p53 negative tumour patients showed a better survival. In this group the median OS was 3.8 years and the DFS was 3.3 years. The above findings have reinforced the view that p53 immunohistochemical detection is of help in detecting a subgroup of breast carcinoma patients who are at high risk. This may also be of particular relevance in decisions regarding adjuvant chemotherapy to these patients.

Antineoplastic Agents↗

Incidental prostate cancer: the importance of complete prostatic removal at cystoprostatectomy for bladder cancer.

Patients with invasive bladder cancer could be at a higher risk for a second malignancy such as an unsuspec- ted prostate cancer. We report a case of muscle-invasive transitional cell carcinoma of the urinary bladder with incidental adenocarcinoma of prostate, and review the literature to highlight the importance of complete prostatic removal to prevent residual disease.

Adenocarcinoma↗