Difference in Risk Factors for Breast Cancer by ER Status in an Indigenous African Population.

Introduction. Breast cancer is the commonest cancer among women globally. In Uganda, it is on the rise, projected at a 4.5% annual ASR increase (age standardized incidence rate). The reasons for this steep increase are not fully established. In the recent past, gene profiling in tumor tissues suggests that breast cancers are divided into subtypes dependent on the presence or absence of oestrogen receptor, progesterone, and human epidermal growth factor receptor 2 (HER 2). These subtypes do have distinctive clinical outcomes and perhaps risk factors from past studies. There is paucity of data on hormonal receptor status and the traditionally known risk factors in sub-Saharan Africa. The purpose of this study therefore was to establish the differences between ER status and the traditionally known risk factors for breast cancer in Uganda. Methods. An observational analytical hospital, based study, carried out at Makerere University, College of Health Sciences. Formalin fixed and paraffin imbedded sections were prepared for haemotoxylin and eosin (H&E) stains and immunohistochemistry (IHC). Ethical approval was obtained. Results. A total of 113 women were recruited. Mean age was 45 years (SD14). There were no significant differences in selected risk factors (setting, age, contraceptive use, parity, breast feeding, or menarche) by ER status although ER negative tumors had significantly higher grade tumors (by a factor of two) compared to ER positive tumors. Conclusion. There were no significant differences among risk factors by ER status contrary to what several other studies suggest. The manifestation of breast cancer in Africa warrants further extensive inquiry.

Hepatitis B virus and HIV infection among patients with primary hepatocellular carcinoma in Kampala, Uganda.

BACKGROUND: Hepatitis B virus (HBV) is the commonest cause of primary hepatocellular (PHC) carcinoma worldwide. Co-infection with the HIV leads to more rapid progression of liver disease. OBJECTIVES: We described prevalence of HBV and HIV among patients with PHC admitted to Mulago Hospital, Kampala, Uganda. METHODS: We assessed all patients admitted to the gastrointestinal service of Mulago hospital with a diagnosis of PHC for HBV and HIV infection. RESULTS: From March to June 2008, we recruited 15 patients. Nine (60%) were male; the overall median age was 32 years (IQR 15 -67), with median ages for male and female 33 and 36 years respectively. Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and AFP were all elevated with median values of 57.5 IU/L, 222 IU/L, 392 IU/L and 362 ng/ml respectively (IQR 14-145, 49-393, 165-1294 and 7-480). Eight (53%) patients were from North and Northeastern Uganda. The HBsAg was reactive in 13(87%) patients and HIV in 3(20%), all of whom were also co-infected with HBV. CONCLUSION: There is high prevalence of HBV and HBV/HIV co-infection among patients with PHC in Uganda with high mortality. Reduction in incidence and mortality due to PHC in Uganda will require urgent large scale HBV vaccination.

Cancer survival in Kampala, Uganda, 1993-1997.

The Kampala cancer registry was established in 1954 as a population-based cancer registry, and registration of cases is done by active methods. The registry contributed data on survival for 15 cancer sites or types registered in 1993-1997. For Kaposi sarcoma, only a random sample of the total incident cases was provided for survival study. Follow-up has been carried out predominantly by active methods, with median follow-up ranging from 4-26 months. The proportion with histologically verified diagnosis for various cancers ranged between 36-83%; death certificate only (DCO) cases were negligible; 58-92% of total registered cases were included for survival analysis. Complete follow-up at five years ranged between 47-87% for different cancers. Five-year age-standardized relative survival rates for selected cancers were Kaposi sarcoma (22%), cervix (19%), oesophagus (5%), non-Hodgkin lymphoma (26%), breast (36%) and prostate (46%). None survived beyond 5 years for cancers of the stomach and lung. Five-year relative survival by age group was fluctuating with no definite pattern or trend emerging and no survivors in many age intervals.

Myelodysplasia in Ugandan patients with HIV/AIDS: an autopsy study.

BACKGROUND: Myelodysplasia has been reported to occur quite frequently in the spectrum of HIV/AIDS disease and is thought to be partly responsible for bone marrow failure in these patients. However, the frequency and type of myelodysplasia appear to differ at different stages of the disease in different populations with mechanisms of its development not well understood. OBJECTIVE: To document the pattern of myelodysplasia in Ugandan patients with terminal HIV/AIDS disease. DESIGN: Prospective descriptive study. SETTING: Department of Pathology, Faculty of Medicine, Makerere University College of Health Sciences SUBJECTS: Bone marrow necropsies from patients who died with AIDS disease at Mulago teaching hospital in Kampala, Uganda during a one-year period. RESULTS: Eighty-four (84%) of the 50 cases studied had myelodysplasia with 39 cases having megakaryocytic myelodysplasia. Myelodysplasia involving erythroid cell series occurred in 23 and in 20 of these cases was in combination with megakaryocytic dysplasia. Granulocyte myelodysplastic features were observed in only two cases and these two cases did not have other cell lines involved. CONCLUSION: Myelodysplastic features are common in HIV patients with megakaryocytic and eythroid cell lines being the most affected. This could be due to the direct HIV effect, or the combined effect of opportunistic infections, neoplasms, drugs and HIV itself affecting the haemopoietic stem cell and or its microenvironment.

Pancreatic cancer in an 18-year-old boy.

We report a case of histopathologically proven pancreatic cancer in an 18-year-old boy. Complete blood picture revealed moderate normochromic normocytic anaemia with anisocytosis. Other laboratory results including liver function tests, renal functions tests, serum amylase, fasting blood sugar level and serum electrolytes were all of normal values. Abdominal US showed a focal mass of the pancreatic body and tail with involvement of the spleen and the transverse colon. Laparotomy confirmed the sonographic findings and demonstrated adhesions of the transverse colon to the mass at the splenic hilum. Histology of the mass showed a well differentiated adenocarcinona of the body and tail of the pancreas. This highlights the differentiation of pancreatic cancer from autoimmune pancreatitis and, to a lesser extent, other forms of pancreatitis and benign pancreatic lesions.

Expression of aldehyde dehydrogenase 1 (ALDH1) is associated with basal-like markers and features of aggressive tumours in African breast cancer.

BACKGROUND: Putative breast cancer stem cells might express surface markers such as aldehyde dehydrogenase 1 (ALDH1) and BMI-1 proteins. The aim of this study was to explore the expression of these proteins in breast cancers from an African population and their associations with the basal-like phenotype (BLP) and other molecular characteristics. METHODS: We analysed 192 paraffin-embedded breast carcinoma samples by tissue microarrays and immunohistochemical methods. RESULTS: In total, 88 tumours (48%) expressed ALDH1, whereas 46 (25%) expressed BMI-1 protein. Expression of ALDH1 was associated with high histological grade (P<0.0005), high mitotic count (P<0.0005), high nuclear grade (P<0.0005), oestrogen receptor (ER) negativity (P<0.0005), progesterone receptor (PR) negativity (P=0.009), p53 expression (P=0.034), cytokeratin 5/6 positivity (P=0.008), epidermal growth factor receptor (EGFR) expression (P=0.015) and the BLP (P<0.0005), whereas it was inversely associated with BMI-1 staining (P=0.009). On the other hand, BMI-1 expression was associated with low histological grade (P=0.004) and ER positivity (P=0.001). CONCLUSION: There was a high prevalence of ALDH1 expression among breast carcinomas and associations with basal markers and features of aggressive tumours. Studies are required to elucidate the importance of these findings for improved understanding of breast cancer biology.

Trends in the incidence of primary liver cancer in Central Uganda, 1960-1980 and 1991-2005.

Primary liver cancer (PLC) incidence trends from Africa are unknown. Using Kampala Cancer Registry data from 1960 to 1980 and 1991 to 2005, we identified 771 PLCs. Although rates were stable among men, PLC incidence among women increased >50%. Investigations of viral hepatitis, aflatoxin, obesity, and human immunodeficiency virus (HIV) may help to explain the increasing incidence of hepatocellular carcinomas (HCCs).

Lymphomas diagnosed in Uganda during the HIV/AIDS pandemic.

BACKGROUND: There are numerous reports from different countries documenting a change in frequency and profile of lymphomas after the onset of the HIV/AIDS pandemic. In Uganda little is known concerning the distribution of lymphoma subtypes diagnosed at the Department of Pathology, Makerere University College of Health Sciences during this period. OBJECTIVE: To examine the frequency and diagnostic profile of lymphomas diagnosed in Uganda in the HIV/AIDS era. DESIGN: Retrospective study. SETTING: Department of Pathology, Makerere University College of Health Sciences, Kampala, Uganda. SUBJECTS: One thousand and thirteen patients diagnosed with lymphomas in the period 1980-1989. RESULTS: The most common type of non-Hodgkin lymphoma was Burkitt lymphoma (36%). The frequencies of lymphocytic and histiocytic types were 34.5% and 8.2% respectively. CONCLUSION: There was a decrease in histopathologically diagnosed lymphomas in Uganda in the period 1980-1989. Burkitt lymphoma continues to be the most common subtype diagnosed, some major lymphoma subtypes like T-cell and follicular lymphomas were not reported in the country in the HIV/AIDS era.

Burkitt's lymphoma in Uganda: the role of immunohistochemistry in diagnosis.

BACKGROUND: Haematoxylin and eosin staining has remained the standard diagnostic method for Burkitt's lymphoma. Ancillary tests including immunohistochemistry, not widely available in developing countries, are important tools in verifying the diagnosis of lymphomas with equivocal morphological findings. OBJECTIVE: To evaluate the reliability of haematoxylin and eosin staining in the diagnosis of Burkitt's lymphoma using immunohistochemistry as the gold standard. DESIGN: Cross sectional study. SETTING: Department of Pathology laboratory, Makerere University Medical School, Uganda. SUBJECTS: One hundred and thirty eight formalin fixed paraffin embedded biopsies of Burkitt's lymphoma diagnosed from January 2001 to December 2005. RESULTS: Of the 138 tumours, 88.4% were extra-nodal: jaw 36.2%, ovary 21%, gastrointestinal tract 12.3% other abdominal 11.6%. Males (55.8%) predominated. The sensitivity and specificity of haematoxylin and eosin were 93.2% and 50% respectively. The positive and negative predictive values were 91.7% and 55.6%. CONCLUSION: Histology using haematoxylin and eosin staining is sensitive in the diagnosis of Burkitt's lymphoma but not very specific. Immunohistochemical staining with CD20, Ki-67 and bcl-2 is necessary for difficult cases.

p53 Expression in Colorectal Carcinoma in Relation to Histopathological Features in Ugandan Patients

Background: It has been shown that colorectal carcinoma is increasing in incidence in African countries. This could be due to change in life style. Molecular patho- genesis of colorectal cancer commonly involves mutation in p53 gene which leads to expression of p53 protein in tumor cells. Expression of p53 protein has been associated with poor clinical outcome and reduced survival in patients. Objective: This was a retrospective laboratory based study carried out in the Department of Pathology Makerere University; Kampala; Uganda. The aim of the study was to evaluate the expression of p53 protein in colorectal carcinoma in Ugandan patients; specifically its association with histological types; degree of differentiation; sites of the tumor and demographic characteristics of the patients. Methods: Immuno- histochemistry was carried out on 109 patient's paraffin embedded tissue blocks of colorectal carcinoma diagnosed in the Pathology Department; Faculty of Medicine Makerere University Kampala during the period 1995 to 2005. The indirect immunoperoxidase method using monoclonal antibody p53 DO-7 and Envision + Dual link system-HRP to detect p53 expression was used. Haematoxylin and eosin stain was used for evaluation of histological types and degree of differentiation of the tumors. Topography of the tumors and demographic data were obtained from accompanying histological request forms. Results: Out of 109 patient's tissue blocks that were studied; 61 cases (56) expressed p53 protein in the nucleus of malignant cells. Right sided colonic tumors were commoner (53.2) than left sided colonic tumors (46.8). p53 protein was expressed more in left sided colonic tumors with a significant difference (p0.05); it was also expressed more in well differentiated tumors and non mucinous adenocarcinomas but with no significant difference (p0.05). p53 expression was not affected by age or sex. Conclusion: Frequency of p53 protein expression in Ugandan patients did not differ from that reported in the other parts of the world. It was expressed more in the left sided colonic tumors and this could support the hypothesis that right and left colonic tumors could have different pathogenesis and probably also responsible for difference in prognosis in these two topographic sites

Substitution of Malachite Green with Nigrosin - Eosin Yellow Stain in the Kato-Katz Method: Microscopical Appearance of the Helminth Eggs

Background:The Kato-Katz thick smear technique is the standard technique recommended by the World Health Organisation for the quantitative diagnosis of Schistosoma mansoni and other intestinal helminth infections.The major problem of the technique is that a few hours after the preparation of slides hookworm eggs over clear and disappear due glycerin. Objective:To illustrate clear visibility of different helminth eggs microscopically in Odongo-Aginya method; substitution of malachite green with 7.5nigrosin in 10formalin and 5eosin in 10formalin. Method: Measured; strained stool specimen was stained with mixture of nigrosin/ eosin and covered with cellophane cover slips.The prepared slide was examined immediately microscopically. Result: Slides prepared with Odongo-Aginya method can be examined immediately or later without compromising the visibility of parasite eggs and larvae. Hookworm eggs remain visible for a long time. Conclusion:The present publication shows microscopic appearance of the helminth eggs using the Odongo-Aginya modification

c-erbB-2 oncoprotein over-expression in breast cancer and its relationship to histology and grade in a Ugandan population.

OBJECTIVE: To evaluate c-erbB-2 oncoprotein over expression in breast cancer patients of Kyadondo county and also relate this oncoprotein to histological type and grade of the tumour. DESIGN: Cross-sectional study. SETTING: Pathology Department, Faculty of Medicine, Makerere University. SUBJECTS: Seventy two breast cancer patients who were among the 174 entered in survival study had their paraffin breast tissue blocks retrieved from archives of Pathology Department and had their c-erbB-2 determined by peroxidase-labeled streptavidin-biotin immunohistochemical method. RESULTS: c-erbB-2 oncoprotein was over expressed in 33.3% of the tumours and correlated positively with histological grade (p = 0.007). TH oncoprotein over expression was not restricted to any particular histological type and there was no association with age of patient. CONCLUSION: The over expression of c-erbB-2 oncoprotein observed in one third of breast cancer patients of this African population could partly explain the observed poor survival rate reported in this community.

Cancer survival in Kampala, Uganda.

Epidemiological data on the occurrence of cancer in sub-Saharan Africa are sparse, and population-based cancer survival data are even more difficult to obtain due to various logistic difficulties. The population-based Cancer Registry of Kampala, Uganda, has followed up the vital status of all registered cancer patients with one of the 14 most common forms of cancer, who were diagnosed and registered between 1993 and 1997 in the study area. We report 5-year absolute and relative survival estimates of the Ugandan patients and compare them with those of black American patients diagnosed in the same years and included in the SEER Program of the United States. In general, the prognosis of cancer patients in Uganda was very poor. Differences in survival between the two patient populations were particularly dramatic for those cancer types for which early diagnosis and effective treatment is possible. For example, 5-year relative survival was as low as 8.3% for colorectal cancer and 17.7% for cervical cancer in Uganda, compared with 54.2 and 63.9%, respectively, for black American patients. The collection of good-quality follow-up data was possible in the African environment. The very poor prognosis of Ugandan patients is most likely explained by the lack of access to early diagnosis and treatment options in the country. On the policy level, the results underscore the importance of the consistent application of the national cancer control programme guidelines as outlined by the World Health Organization.

Epidermodysplasia verruciformis human papillomavirus types and carcinoma of the conjunctiva: a pilot study.

A total of 21 squamous-cell carcinoma of the conjunctiva (SCC) and 22 control subjects had conjunctival samples tested for human papillomavirus (HPV) types using PCR-based assays. Epidermodysplasia verruciformis HPV types were found in 86% of SCC cases and 36% of control subjects (Odds ratio=12.0), suggesting a role of HPVs in the aetiology of SCC.

Human papillomaviruses and cancer in Uganda.

In a case-control study in Uganda, we examined associations between different cancer sites or types in relation to antibodies against human papillomaviruses (HPV)-16, -18 and -45. For each cancer site or type, the control group comprised all other cancers excluding those known, or thought to be associated with HPV infection (cancers of the uterine cervix, penis and eye). Among controls the seroprevalence of antibodies was 11% (68/616) against HPV-16, 5% (29/605) against HPV-18 and 6% (35/605) against HPV-45. Antibodies against HPV-16 were significantly associated with only two cancers: uterine cervix [prevalence of antibodies 27% (51/191); odds ratio (OR) 2.0, 95% confidence interval (CI) 1.2-3.1, P=0.01] and penis [prevalence of antibodies 27% (4/15); OR 6.4, 95% CI 1.7-24.3, P=0.01]. For both cancers, the risk increased with increasing anti-HPV-16 antibody titre (Ptrend=0.01 for each). No cancer site or type was significantly associated with antibodies against HPV-18 and -45.

Takayasu's arteritis (pulseless disease) in Uganda.

We report herein the case of a 23 year old woman who was referred to Mulago National Referral and Faculty of Medicine Makerere University Teaching Hospital because of sudden collapse, left sided weakness and headache for management. The patient underwent a battery of investigations but died five days after admission. The post mortem findings were extensive infarction the right cerebrum extending from parietal to occipital lobes. There was thickening of the wall and complete obliteration of right common carotid artery. The left common carotid artery was severely stenosed with marked thickening of the wall. The subclavian artery was thickened and completely obliterated. Microscopically there was intimal thickening by fibrous connective tissue and infiltrate of chronic inflammatory cells in the walls of the three affected branches of the oarta. These gross microscopic features were compatible with Takayasu's arteritis (TA).

Survival of cervix cancer patients in Kampala, Uganda: 1995-1997.

The survival experience of 261 patients with cancer of the cervix registered by the Kampala population-based cancer registry, Uganda, in 1995-1997, is described. Vital status of the subjects was established by active methods including a search of hospital records and house visits. Of the 261 cases, 82 (31.4%) were dead and 105 (40.2%) were alive at the closing date of 31 December 1999; the remaining 74 cases (28.4%) were lost during the follow-up period. Overall observed and relative survival at 3 years was 52.4 and 59.9%, respectively. Of these cases, one-quarter (63) had been treated in the radiotherapy department. These cases had better survival (82.6%) than nontreated patients (78.5%) after 1 year of follow-up, but there was no difference at 3 years. HIV status was not significantly related to prognosis. Stage is an important determinant of survival: cases with distant metastasis had a risk of death some three times that of patients with localised disease. Early detection and prompt treatment should improve overall survival from cervix cancer, in the African context.

Infection with Kaposi's sarcoma-associated herpesvirus (KSHV) and human immunodeficiency virus (HIV) in relation to the risk and clinical presentation of Kaposi's sarcoma in Uganda.

A case-control study from Uganda found that the risk of Kaposi's sarcoma increased with increasing titre of antibodies against Kaposi's sarcoma-associated herpesvirus (KSHV) latent nuclear antigens, independently of HIV infection. Clinically, widespread Kaposi's sarcoma was more frequent among patients with HIV infection than in those without, but was not related to anti-KSHV antibody titres.

Haematoxylin and eosin staining in the diagnosis of Hodgkin's disease in Uganda.

BACKGROUND: Whereas immunohistochemical methods have been widely used for the diagnosis and classification of Hodgkin's disease in the developed countries, there are very few reports of their use in the developing countries where haematoxylin and eosin is the mainstay of diagnosis of Hodgkin's disease. Yet the diagnostic accuracy of haematoxylin and eosin has not been assessed in Uganda. OBJECTIVE: To determine the reliability of haematoxylin and eosin staining in the diagnosis of Hodgkin's disease using immunohistochemistry as the reference standard. DESIGN: Laboratory based cross sectional study. SETTING: Makerere University Medical School, Department of Pathology. METHODOLOGY: Two hundred and forty formalin fixed, paraffin embedded biopsies seen in the Makerere University, Department of Pathology from 1980-2000 were studied. The tissue sections, were assessed and subjected to immunohistochemical methods using monoclonal antibodies including leucocyte common antigen, LCA (CD45), antibodies to Reed-Sternberg cells (CD15, CD30) and antibodies to B cells (CD20). The sensitivity, specificity, positive predictive value and negative predictive value were assessed. The overall Kappa score was used to assess the agreement between the two diagnostic tests. RESULTS: Of the 240 biopsies, 171(71.3%) were confirmed as Hodgkin's disease by immunohistochemistry. Using haematoxylin and eosin (H&E), only 131 of the 171 cases of Hodgkin's disease were detected. The mean age of the 171 cases was 26.1 (SD 16.2) years, with a mode of 20.0 and median of 22.5 years. The 15-24 year age group was the most affected (47.2%). There were more males (65.9%) than females and most were Baganda the dominant tribe in the central region. The sensitivity, specificity, positive and negative predictive values of haematoxylin and eosin were 76.61%, 92.75%, 96.32% and 61.53% respectively. The agreement between the two tests was 81.25% with an overall measure of agreement, Kappa, of 0.602. CONCLUSION: Haematoxylin and eosin has relatively high efficacy in the diagnosis of Hodgkin's disease. Use of haematoxylin and eosin is still recommended for the diagnosis of Hodgkin's disease, reserving the expensive immunohistochemistry for difficult cases.