CORRELATIONSHIP OF CATHEPSIN D AND TOPOISOMERASE II ALPHA WITH NUCLEAR GRADING IN BREAST CANCERS.

56 cases of infiltrating duct carcinoma of the breast were studied for the expression of cathepsin D and topoisomerase II alpha. The results were correlated with the morphological differentiation, as determined by the Nottingham's modification of the Bloom-Richardson system. Cathepsin D posltivity in tumour cells and stromal cells was seen in 44.6% and 55.4% cases respectively, whereas topoisomerase II alpha positivity was seen in 33.9% cases. In grade II tumours cathepsin D in tumour cells and stromal cells was 44.4% and 47.2% respectively, as compared to 27.8% posltivity for topoisomerase II alpha. The corresponding figures for grade III tumours were 50.0%, 79.6% and 64.3 % respectively. As grade I comprised only 3 cases no statistical correlation could be observed. It is evident that with increase in tumour grade there is a statistical increase in expression of cathepsin D, a lysosomal acidle protease-implicated in the process of tumour invasion and metastasis, and of topoisomerase II alpha, a marker of rapid cell proliferation and aneuploidy.

Spectrum of renal lesions in HIV patients.

BACKGROUND: A variety of renal lesions have been reported in HIV positive patients from western world however there is paucity of Indian data. METHODS: Over a four year period, all hospitalised HIV positive patients were screened for renal involvement. Screening was done with urinalysis. Those with abnormality in urine examination underwent further assessment with clinical, biochemical, immunological profile and renal biopsy. Renal histology was studied by light and electron microscopy. RESULTS: Twenty-five (17.6%) of the 142 patients screened, had proteinuria/abnormal urinary sediment however none of the patient had proteinuria in nephrotic range. Fourteen of these 25 patients were asymptomatic while others had AIDS. Renal biopsy was studied by light microscopy in all and by electron microscopy in 11 cases. On histology mesangioproliferative GN was encountered in eight, focal segmental glomerulosclerosis in four and collapsing GN in one patient. In two cases cryptococcal infiltration and in one lymphomatous deposits were seen in glomerulus and interstitium. In one patient interstitium showed granulomas and in other three mononuclear cell infiltration. Histology was normal in 8 (32%) patients. On EM visceral cell hyperplasia and vacuolisation was seen in all, two had collapse of glomerular basement membrane and in three cases tubuloreticular structures were seen. There was no co-relation of renal histology with duration or severity of the disease (p > 0.05). No deterioration of renal function was seen over a short follow up period of 4.2 months (1-20 months). CONCLUSION: This study highlights that HIV patients exhibiting abnormal urinary sediment usually have underlying renal lesion and at times unexpected opportunistic infections may be present.

SPECTRUM OF NEPHROPATHIES WITH SPECIAL REFERENCE TO PRIMARY GLOMERULOPATHIES.

A retrospective study was carried out where histopathology records of Department of Pathology, Armed Forces Medical College, Pune were scrutinised covering a period of 10 years. We came across 325 cases of nephropathies. The sample comprised of 92.6% adults and 7.4% children. 79.7% were males and 20.3% were females. The patient population comprised of 35.1% serving soldiers, 37.8% their family members and 27.1% not related to Armed Forces. The study is based on only light microscopy findings. It was observed that primary glomerular disease was the commonest entity and comprised of 61.5% of all the nephropathies. Acute diffuse proliferative glomerulonephritis was not only the commonest primary glomerulopathy (23.5%) but the commonest nephropathy as well. The other primary glomerulopathies in descending order of frequency were, membranoproliferative glomerulonephritis (22.5%), mesangioproliferative glomerulonephritis (21.5%), chronic glomerulonephritis (9%), minimal change disease (7.5%), membranous glomerulopathy (7%), focal segmental glomerulosclerosis (5%) and crescentic glomerulonephritis (4%). We had only 14 cases (4.3% of all nephropathies) of secondary glomerulopathies, amongst which amyloidosis was the commonest cause. We came across 2 cases (0.6% of all nephropathies) of Alport's syndrome. In the other nephropathies, 22.2% were tubulointerstitial diseases and 5.5% were malignant kidney tumors. In 5.8% renal biopsies, no significant pathology was seen on light microscopy.

CORRELATIONSHIP OF HORMONE RECEPTOR STATUS, p53 MUTATION AND c-erb B-2 OVEREXPRESSION WITH NUCLEAR GRADING IN BREAST CANCERS.

Thirty cases of infiltrating duct carcinoma of the breast were studied for the expression of estrogen receptor (ER) and progesterone receptor (PR) status; p 53 protein mutation and c-erb B2 overexpression. The results were correlated with the morphological differentiation, as determined by the Nottingham's modification of the Bloom-Richardson system. Hormone receptor positivity was seen in 46.67% cases, whereas p 53 mutation and c-erb B2 overexpression were seen in 50.00% and 60.00% cases respectively. In grade II tumours receptor positivity, p53 mutation and c-erb B-2 overexpression were 57.15%, 42.85% and 52.38% respectively. The corresponding figures for grade III tumours were 33.33%, 83.33% and 66.67% respectively. As grade 1 comprised only 3 cases no statistical correlation could be observed. Thus we conclude that receptor positivity declined, whereas p 53 mutation and c-erb B-2 overexpression increased, with increase in tumour grade.

IMPROVED ACCURACY RATES OF FNAC INTERPRETATION IN BENIGN BREAST LESIONS.

We carried out a retrospective study of 194 biopsy proved benign breast lesions comparing the fine needle aspiration cytology (FNAC) diagnosis offered earlier. We reviewed the cytology smears based on recently advocated criteria and offered our fresh diagnosis. It was observed that we still overdiagnosed five cases of fibroadenomas and underdiagnosed four cases of fibrocystic change. However the quantum of such discrepancies decreased considerably than seen earlier. We could correctly diagnose two tubular adenomas and two intraductal papillomas. We also reduced the number of nonspecific diagnosis of benign breast disease from 24 to 08. Hence we could register an overall improvement of accuracy rate to 84.5% as compared to 58.8% achieved earlier.

AN OVERVIEW OF PROGNOSTIC MARKERS IN BREAST CANCER.

For many years axillary lymph nodes metastasis was the most important prognostic factor to predict the overall and disease free survival and guided the oncologists for institution of chemotherapy in breast cancer cases. However this factor alone or in combination with other parameters like, age of the patient, tumour size, histological type and tumour grade failed to predict the prognosis accurately in number of these cases. In pursuit to achieve the perfection, many new parameters which are biological or molecular in nature have been discovered. It is claimed that these factors not only have the capability to predict the prognosis but are also able to identify 'high risk' group of patients. However analysing all these parameters in a given case is not only cost prohibitive but also not essential. In order to solve this problem few important biological parameters have been reviewed, which are considered to cover all the important facets of the breast cancer. The parameters reviewed are ER, PR, S phase fraction, DNA ploidy, MIB-1 antibody, p53, C-erb-2, nm23, Cathepsin, Topoisomerase II alpha.

Primary cranial Ewing's sarcoma.

Primary Ewing's sarcoma of the cranium is extremely rare, with only 17 cases reported so far. We describe a further case with involvement of the frontotemporal region and the orbit. The patient, an adult male, was admitted with headache and papilloedema, and later developed localised swelling and proptosis. He was treated with surgery, radiotherapy and chemotherapy, and was free from metastases during a follow-up of 14 months. The prognosis of Ewing's sarcoma is improving with radiotherapy and chemotherapy. Further cases are needed to study the biological behaviour of primary cranial Ewing's sarcoma.

Cerebellopontine angle metastasis from clear-cell renal carcinoma presenting as bleeding from the ear.

Metastatic lesions in the cerebellopontine angle are rare. We encountered one such metastatic lesion from clear-cell renal carcinoma that had a striking clinical appearance, bleeding from the ear and multiple lower cranial nerves' involvement. While the overall prognosis in CNS metastasis from systemic malignancy is gloomy, useful palliation can be achieved in patients with solitary lesions.

AGAROSE GEL ELECTROPHORESIS AS SCREENING TEST FOR MULTIPLE MYELOMA CASES.

OBJECTIVE: To study effectiveness of agarose gel electrophoresis as a screening tool for early detection of multiple myeloma. DESIGN: A prospective study in OPD setting. PATIENTS: Two hundred and nineteen patients (126 females and 93 males) in the age group of 28-82 year referred to Department of Physical Medicine and Rehabilitation from various departments for treatment of unexplained pains and aches (with or without osteoporosis). They had been investigated and were adjudged organic disease free. INTERVENTION: Agarose gel electrophoresis was carried out on sera of these patients. Bone marrow aspiration was done for all those patients whose serum showed a monoclonal protein peak. Characterisation of M peak was also carried out by Immunoelectrophoresis. MAIN RESULT: Out of the 219 patients, sera of 29 patients showed a monoclonal protein peak. Immunoelectrophoresis and bone marrow aspiration confirmed the diagnosis of multiple myeloma in these patients. 17 were male and 12 were female patients. All of them were over 50 years of age. CONCLUSION: Agarose gel electrophoresis was found to be very sensitive test for early detection of multiple myeloma cases. Hence it was strongly recommended to be used as a screening test for all elderly people who present with unexplained aches and pains with or without osteoporosis.

CAN IMMUNOHISTOCHEMISTRY DISTINGUISH BETWEEN PRIMARY AND METASTATIC HEPATIC CARCINOMA?

OBJECTIVE: To determine if immunohistochemistry is useful to distinguish between primary and metastatic hepatic carcinoma. STUDY DESIGN: Cases of hepatocellular and adenocarcinoma of liver from surgical and autopsy pathology files as diagnosed on routine histopathology with the help of haematoxylin-eosin stain. PATIENTS: Thirty four patients with hepatic space - occupying lesions (a single lesion in 6 patients, multiple lesions in 5 patients and unspecified in remaining 23 patients). The histopathology diagnosis included 14 hepatocellular carcinoma (HC), 10 cholangiocarcinoma (CC), 7 metastatic carcinoma (MC) (colonic: n=4, pancreatic: n=2, mammary: n=l) and three cases were unclassified. INTERVENTION: The paraffin embedded blocks of biopsy and autopsy cases were taken out and sections of 4 µm thickness were cut. The immunohistochemistry staining was carried out by using a panel of 7 monoclonal antibodies. The monoclonal antibodies which were used were as follows - a fetoprotein (AFP), α 1 antitrypsin (AAT), monoclonal carcinoembryonic antigen (MCEA), myelomonocytic antigen (Leu-Ml), tumour associated glycoprotein (B72-3), A-subunit coagulation Factor XIII (Factor XIIIa) and blood group substance (Lex). MAIN OUTCOME MEASURES: Sections were defined as immunohistochemically 'positive' if definitive crisp labelling was seen in atleast 10% of tumour cells by two observers. The positive staining was classified as either predominantly cytoplasmic or membranous or both. The presence or absence of nuclear staining was also noted. MAIN RESULTS: The typical immunoreactivity of HCs included positivity for AAT, AFP and factor XIIIa and no staining for B 72-3 and Leu-Ml. Of 14 patients who were originally diagnosed as having HC, AAT was expressed in 86% and AFP was expressed in cytoplasm in half of the patients. Factor XIIIa displayed cytoplasmic reactivity in 71% cases of HC. Lex was present focally in 3 cases of HC, as was monoclonal CEA. These 3 cases showed features of hepatocholangiocarcinoma. In all 10 cases of CC there was staining for both Leu-Ml and Lex. The pattern of reactivity was cytoplasmic for Leu-Ml and it was both cytoplasmic and membranous for Lex. In 6 cases there was expression of B72-3 and monoclonal CEA in cytoplasm. None of the cases of CC showed staining for AFP and AAT only one case showed staining for AAT and factor XIIIa. As far as MC is concerned, there was expression of both Leu-M, and Lex in a cytoplasmic distribution in all the seven cases. The membranous accentuation of Lex seen in all cases of CC was not present in the cases of MC. Four of the 7 cases of MC showed reactivity for B72-3 as well and the staining pattern of Leu-M, and B72-3 was predominantly both cytoplasmic and membranous. In 3 of the 7 cases of MC, there was expression of monoclonal CEA, in 1 case there was expression of AAT and in 2 cases there was expression of factor XIIIa. CONCLUSIONS: Histologic differentiation of HC from CC and MC can be greatly aided by immunohistochemical studies. Using a panel of 7 antibodies, cases of HC displayed cytoplasmic reactivity for AAT, AFP and factor XIIIa. Cases of CC showed membranous and cytoplasmic reactivity for Lex but only cytoplasmic reactivity for Leu-M, and B72-3. On the other hand cases of MC showed only cytoplasmic staining but not membranous accentuation for Lex but Leu-M, and B72-3 showed membranous as well as cytoplasmic staining. The antibody MCEA showed variable results and hence was considered not useful. Therefore the results strongly suggest that a panel of 6 monoclonal antibodies (except MCEA) will greatly help in differentiating between primary and metastatic carcinoma.