Immunohistochemical Expression Of Matrix Metalloproteinase-1 (MMP-1) in Different Types Of Breast Carcinoma And Its Comparison With ER/PER and HER2/neu.

BACKGROUND: Breast cancer is a complex disease that comprises of various biological sub-types with different natural history. Matrix metalloproteinase-1(MMP-1) expression has been reported to inversely correlate with the survival. The current study was conducted to classify breast cancer into four subtypes based on IHC, to assess the immunohistochemical expression of MMP-1 in primary breast carcinoma, to compare its expression with ER/PR and HER2/neu. METHODS: A descriptive study was conducted on 100 mastectomy specimens of breast carcinoma after being fixed in 10% formalin at Department of Histopathology, University of Health Sciences Lahore. Sections were taken on frosted slides for H&E and on lysine coated slides for immunohistochemistry (IHC). Haematoxylin and eosin (H&E) and IHC for oestrogen receptor/progesterone receptor (ER/PR), HER2/neu and Matrix metalloproteinase (MMP-1) were performed according to protocol. RESULTS: The mean age was 48.4411.79 Years (ranging 25 to 90 years). 97 cases were of Invasive ductal carcinoma (IDC) type, two showed the features of invasive lobular carcinoma and only one case was found to be of mucinous type, 19 cases were found to be in grade I, 74 in grade II and seven cases were in grade III. Breast cancer has been classified into four major groups based on IHC profile ER/PR and HER2/neu expression. The groups were: Triple positive, ER/PR+, HER2-, ER/PR-, HER2/neu+ and triple negative) cases. Among 100 cases of breast cancer, 9 were of triple positive type, (ER/PR +, HER2/neu+), 28 cases were of ER/PR +, HER2- type, 19 were ER/PR-, HER2/neu +ve and 44 cases were of triple negative type (ER/PR-, HER2/neu-ve). 13 cases were of score 1 MMP-1out of which 7 (25.0%) were ER/PR+, HER2-, 1 (5.3%) case was ER/PR-, HER2/neu +ve and 5 (11.4%) cases were triple negative. Among 30 cases of MMP-1 score 4, 5(55.6%) cases were of triple positive type, 3 (10.7%) cases were of ER/PR +, HER 2/neu-ve type, 12(63.2%) cases were of ER/PR-, HER 2/neu+ve type, and 10 (22.7%) cases were of triple negative type. A significant p-value of <0.05 was obtained. CONCLUSIONS: Among four IHC based subtypes, most frequent were triple negative breast cancers which showed high IHC score of MMP-I which is reported to be an important marker for metastatic potential in breast carcinoma.

Expression of Bcl-2 in Primary and Recurrent Odontogenic Keratocysts in Comparison with Other Odontogenic Lesions.

PURPOSE: To determine the biological behaviour of common odontogenic cystic lesions by analysing and comparing bcl-2 expression amongst them. MATERIALS AND METHODS: Our study covered 90 formalin fixed paraffin embedded tissue samples: 26 primary cases each of radicular cysts (RC), dentigerous cysts (DC) and odontogenic keratocysts (OKC) and 12 of recurrent OKCs. Bcl-2 expression was analysed immunohistochemically and data analysis was accomplished using SPSS version 17.0. Means were taken for age while for gender and site of the lesions frequencies and percentages were determined. The Chi-square test was applied to evaluate any statistically significant difference of bcl-2 expression in these lesions and p value of ≤0.05 was taken as significant. RESULTS: All the recurrent OKCs showed a strong positivity for bcl-2 that was absent in all of its primary cases (p value<0.05). Although variation in expression of bcl-2 was not found to be statistically significant between RC and DC, however, it became significant when all primary cases of these common odontogenic lesions were compared. CONCLUSIONS: Recurrent OKC showed comparatively a more aggressive behaviour than their primary counterparts and also from RC and DC. Bcl-2 proved to be a valuable adjunct in determining aggressive biological behaviour of odontogenic lesions.

Clinicopathological evaluation of odontogenic tumours in Pakistan - a seven years retrospective study.

BACKGROUND: The purpose of the study was to analyse the clinicopathological spectrum of benign and malignant odontogenic tumours (OT) in Pakistan. MATERIALS AND METHODS: This retrospective study was carried out at the Armed Forces Institute of Pathology (AFIP) Rawalpindi. Seven years archival records of histologically diagnosed odontogenic tumours, both benign and malignant, were collected and the lesions re-diagnosed histologically in accordance with the WHO classification of head and neck tumours (2005). Clinical as well as histological data were analysed and frequency of each type of OT was calculated using computer software programme SPSS (version 17). Mean tumour size was calculated and Chi-square test was applied to find associations of age, gender and site with each histological type of tumour. RESULTS: Only 1.7% of the odontogenic tumours diagnosed in this said period were malignant while the remaining 98.3% were benign. Amongst benign lesions, ameloblastoma was the most common (61.3%) type while primary intraosseous squamous cell carcinoma (1.7%) was the only reported malignant tumour. Mean age of the affected patients was 31.7±16.7 years with posterior mandible as the commonest site involved. CONCLUSIONS: Our study revealed ameloblastoma and primary intraosseous squamous cell carcinoma as the commonest diagnosed benign and malignant tumours respectively. There was a significant difference in age and site of origin of different types of OT at the time of their presentation. However, all the tumours showed male predominance.

Xeroderma Pigmentosum - a disfiguring disease: Single patient with 5 simultaneous tumors on face.

Xeroderma pigmentosum is an uncommon inherited autosomal recessive disorder. Affected patients have a 2000-fold amplified risk of skin cancer. There is an inability to repair the damage to genetic material caused by ultraviolet light. Basal cell carcinoma is the most commonly associated carcinoma followed by squamous cell carcinoma and melanoma. It is a highly mutilating disorder where occurrence of multiple cancers and repeated surgical treatments result in serious psycho-social implications. We present a case of diagnosed xeroderma pigmentosum in a 25 year old male who presented with multiple lesions and non-healing ulcers on face. Four surgical specimens from left lower eyelid, chin, right cheek and upper lip were taken for histopathological diagnosis. Microscopic examination revealed five different tumors from biopsies of these sites - specimen from right cheek revealed two morphologically distinct tumors. The tumors include basosquamous carcinoma, nodular basal cell carcinoma, adenoid basal cell carcinoma, malignant melanoma and cavernous hemangioma.

The role of mast cells and angiogenesis in well-differentiated oral squamous cell carcinoma.

OBJECTIVE: Neo-vascularization is vital for an expansion and metastasis of a tumor and is influenced by a number of mediators. Mast cells are believed to release many pro-angiogenic mediators that may help in tumor expansion and invasion. This study describes the role of mast cells and angiogenesis in oral squamous cell carcinoma (OSCC). STUDY DESIGN: It was a prospective study in which 37 biopsies of well-differentiated OSCC were obtained. Micro-vessels were stained with cluster of differentiation (CD)-34 and mast cells were counted using the Toluidine blue stain. RESULTS: When compared to normal oral mucosal tissue, it was seen that micro-vessel density and mast cell density indeed increases significantly in squamous cell carcinoma; however, they are not correlated to each other. CONCLUSION: This study reports that angiogenesis does increase in OSCC and mast cells also invade the peri-tumor tissue, but they are not directly correlated.

Association of immunohistochemically defined molecular subtypes with clinical response to presurgical chemotherapy in patients with advanced breast cancer.

Gene expression profiling (GEP) has identified several molecular subtypes of breast cancer, with different clinico-pathologic features and exhibiting different responses to chemotherapy. However, GEP is expensive and not available in the developing countries where the majority of patients present at advanced stage. The St Gallen Consensus in 2011 proposed use of a simplified, four immunohistochemical (IHC) biomarker panel (ER, PR, HER2, Ki67/Tumor Grade) for molecular classification. The present study was conducted in 75 newly diagnosed patients of breast cancer with large (>5cm) tumors to evaluate the association of IHC surrogate molecular subtype with the clinical response to presurgical chemotherapy, evaluated by the WHO criteria, 3 weeks after the third cycle of 5 flourouracil, adriamycin, cyclophosphamide (FAC regimen). The subtypes of luminal, basal-like and HER2 enriched were found to account for 36.0 % (27/75), 34.7 % (26/75) and 29.3% (22/75) of patients respectively. Ten were luminal A and 14 luminal B (8 HER2 negative and 6HER2 positive). The triple negative breast cancer (TNBC) was most sensitive to chemotherapy with 19% achieving clinical-complete-response (cCR) followed by HER2 enriched (2/22 (9%) cCR), luminal B (1/6 (7%) cCR) and luminal A (0/10 (0%) cCR). Heterogeneity was observed within each subgroup, being most marked in the TNBC although the most responding tumors, 8% developing clinical-progressive-disease. The study supports association of molecular subtypes with response to chemotherapy in patients with advanced breast cancer and the existence of further heterogeneity within subtypes.

Angiogenesis and mast cell density as predictors of patient survival in squamous cell carcinoma of lung.

BACKGROUND: Measuring the microvascular and mast cell density in squamous cell carcinoma of lung and correlating them with the patient survival may be helpful to guide the use of cancer chemotherapeutic agents which target molecular mechanisms of tumour angiogenesis and mast cells. MATERIALS AND METHODS: It was an observational study. It included 39 newly diagnosed, adult patients of pulmonary squamous cell carcinoma. Angiogenesis was determined by Chalkley's method after immunohistochemical staining of micro-vessels with CD34. Mast cells per HPF were counted in Tolouidine blue stained sections. RESULTS: Mean age of the patients was 58.33 ± 9.14 years. Male to female ratio was 9:1. Most (92.3%) patients were current smokers. Majority of tumours (71.8%) were localised to major bronchi and/or near to hilum and many of them (74.4%) were poorly differentiated. Mean micro-vascular density was 11.80 ± 3.66 per HPF which showed strong negative correlation (r = -0.481, p =0.002) between microvascular density (MVD) and tumour grade. Mean mast cell density was 1.60 ± 2.04 which showed strong negative correlation (r=-.683, p =0.0001) with grade. Angiogenesis and mast cell density were found to be positively correlated (r=0.439, p =0.005). High MVD, but not the MCD was associated with poor survival. CONCLUSION: Angiogenesis and mast cell density are positively correlated with each other however; only high MVD is associated with decreased survival. Thus, the anti-angiogenic agents may be useful in squamous cell carcinoma lung, especially the well differentiated tumours.

The reno-protective effect of aqueous extract of Carum carvi (black zeera) seeds in streptozotocin induced diabetic nephropathy in rodents.

To assess the effect of aqueous extract of Carum carvi seeds in experimentally induced diabetic nephropathy (DN) in rodents, we studied 48 adult male Wistar rats divided into 4 groups: normal controls (group A), diabetes positive control (group B), and experimental (groups C and D). They received Carum carvi extract as a renoprotective agent. Rats having fasting blood glucose levels over 280 mg/dL were included in this study. Group C rats received STZ (60 mg/kg) and aqueous extract of Carum carvi at 30 mg/kg of body weights. On the other hand group D rats received STZ (60 mg/kg) and aqueous extract of Carum carvi at 60 mg/kg of body weight. Blood samples were collected on the 60 th day, and kidneys were also extracted for examination. The diabetic group rats showed a variable increase in the serum levels of glucose, urea, creatinine, total urinary protein and microalbuminuric levels. Body weight decreased and urine volume increased in the diabetic groups. 30 mg/kg body weight of Carum carvi dose decreased the levels of these parameters in rats. On the other hand, 60 mg/kg body weight of Carum carvi dose significantly decreased the levels of the biochemical parameters. The morphological examination of group C rats showed no changes whereas the rats in group D showed moderate changes. Carum carvi constituents, especially flavonoids and carvone have strong anti-oxidant activity, which provides reno-protection against diabetes and its complications. In conclusion, high dose of Carum carvi aqueous seeds extract (60 mg/kg) showed reno-protection against STZ induced dia-betic nephropathy in rats.

Morphological evaluation of colorectal carcinoma with grading staging and histological types.

OBJECTIVE: To evaluate the morphology, grading and staging of colorectal carcinoma (CRC) and to assess the relationship between these parameters. METHODS: This cross-sectional study was carried out at the Departments of Pathology, University of Health Sciences and Sheikh Zayed Federal Post Graduate Medical Institute Lahore, Pakistan, over a period of one year. The study consisted of 100 colectomy/hemicolectomy specimens, received fixed in 10% formalin. The specimens were examined grosslyto observe the various macroscopical features of tumours. Haematoxylin and Eosin stained slides were examined to determine the histological type, grade and stage of CRC. RESULTS: Among the 100 cases, 59 were non mucinous adenocarcinomas, of which 4 were in Dukes' stage A, 51 were in Dukes' stage B and 4 were in Dukes' stage C. Cases of nonmucinous CRC of grade I to grade II were 55 in number. In thirty cases of mucinous carcinomas, 18 were in Dukes' stage B and 12 were in Dukes' stage C, of these 2 were of grade I, 20 were of grade II and 8 were of grade III. All the 11 signet ring cell carcinomas were of grade III and in Dukes' stage C. CONCLUSION: Mucin secreting and signet-ring cell adenocarcinomas of colon and rectum are high grade tumours and presented at an advanced stage.