Molecular detection of the mammaglobin expression in the peripheral blood of Thai breast cancer patients.

Mammaglobin (hMAM) is expressed exclusively in the mammary glands of adult woman and mammary tumour cell lines. Thus, we examined hMAM expression as a market for the detection of carcinoma cells in the peripheral blood of patients with breast cancer in Thailand. In addition, we studied the correlation between hMAM expression in circulation mammary carcinoma cells and clinicopathological prognostic factors of breast cancer. Blood sample obtained from two hundred breast cancer patients at various stages of their disease and from sixty females without breast cancer (thirty healty individuals and thirty patients with various malignancies other than breast cancer) were screened for hMAM mRNA by a nested reverse transcriptase polymerase chain reaction (RT-PCR) assay. We found significant differences between patients with breast cancer and those with other malignancies or healthy controls. None of the samples from the peripheral blood of sixty females without breast cancer was positive, whereas sixty four (32%) of the two hundred sample from breast cancer patients tested positive for hMAM mRNA. While our hMAM nested RT-PCR approach has 100% specificity, its sensitivity is only 32%. The presence or absence of hMAM expression in these breast cancer patients was not associated with clinicopathological prognostic factors including stage, oestrogen and progesterone status, lymph node metastases, histological type, tumour size, differentiation, lymphatic invasion, vascular invasion, menopausal status or age. We summarized that the hMAM nested RT-PCR assay may be an effective tool for the detection of circulating mammary carcinoma cells of breast cancer patients. Nevertheless, the clinical relevance hMAM RT-PCR based tumour cell detections should be further evaluated in prospective studies.

Breast cancer: A cost analysis study.

Objective : To compare the unit cost and the reimbursement calculated by Thai Diagnosis Related Group (DRG) version 3 of breast cancer treatments. Methods: thirty nine breast cancer patients who were underwent surgery during1 March 2001 to 30 April 2001 were sequentially selected. Hospital charts were reviewed. History before diagnosis, type of treatments, laboratory details, hormonal therapy and other costs were recorded. Labor cost, material cost and capital cost were calculated as direct cost which also included the cost of doctor visits. Indirect costs included the cost of the facility. Unit cost of each patent was calculated and compared to the reimbursement calculated by Thai DRG version 3 (September 2002). Results : Of 39 breast cancer patients, total Relative Weight (RW) was 54.37 (mean + SD=1.39+0.23) with full cost being 849,377.52 baht (mean + SD = 21,778.91+8,890.46). The total calculated reimbursement was 869,868.80 baht (men + SD 22,304.33 + 3,635.17). Calculation of reimbursement was based on the initial agreement that the university hospital would receive 16,000 baht in payment per 1 RW. Overall reimbursement was slightly higher than cost. Our study resulted in the classification of patients into 4 DRG groups as follows :1) DRG 09010 (Total mastectomy for malignancy, no complication), 2) DRG 09012 (Total mastectomy for malignancy, with mild to moderate complication),3) DRG 09014 (Total mastectomy for malignancy, with severe complication) and 4) DRG 09020 (Subtotal mastectomy for malignancy, no complication or Conservative breast surgery).Reimbursement was lower than cost in groups 2 and 4. In group 2,1 out of 2 patients had a long hospital stay which resulted in a high average cost. Conversely, unit cost of group 4 was not different from other groups but the RW given was lowest, which made the reimbursement much lower than real cost. Conclusion : In conservative breast surgery (group 4), patients must receive both surgical and radiation treatment to decrease the morbidity which increases the cost of treatment. An increased RW should be specially considered for this group.

Estrogen receptor-alpha mRNA in primary breast cancer: relationship to estrogen and progesterone receptor proteins and other prognostic factors.

The estrogen receptor (ER)-alpha protein and ER mRNA were measured in 314 primary breast cancer patients by enzyme immunoassay (EIA) and reverse-transcription polymerase chain reaction (RT-PCR) assay, respectively. The positivity of ER protein was 53% while of ER mRNA was 37.6%. A significant positive association between ER phenotype and ER mRNA was observed (r = 0.40, p < 0.0001) with a positive-negative agreement between them of 71.8%. The percentage of ER-negative, progesterone receptor (PR)-positive breast tumors was 1.9% by EIA and 7% by RT-PCR assay. This may indicate a difference in ER variants in these studied patients. The ER protein and ER mRNA status were inversely related to tumor size and p53 positivity. Also, ER protein was frequently positive in patients with a higher number of lymph node invasions, well to moderate nuclear differentiated tumor cells and negative c-erbB-2 status. The difference of the ER or ER mRNA status regarding ages, menopausal status, tumor stages and histological types was not shown. In the present study, ER mRNA did not demonstrate a closer relationship to prognostic indicators of breast cancer than ER protein. Before including the ER mRNA assessment in routine investigations of breast cancer, its relationship to prognostic factors and survival outcome should be further assessed with a higher number of patients and a longer follow-up time.

Expression of p53, c-erbB-2 and cathepsin D in relation to hormone receptors in primary breast cancer.

The immunohistochemical expression of p53, c-erbB-2, and cathepsin D oncogene proteins was examined in 494 primary breast carcinomas. This study aimed to investigate an association of expression of these three proteins with other variables known to be related to poor prognosis as well as with 5-year disease free survival (DFS). P53, c-erbB-2, and cathepsin D alone or in combination was negatively correlated with the presence of estrogen and progesterone receptors in breast cancer tissues. Alteration of these oncogenes rendering an expression of the proteins may affect the synthesis of steroid receptor proteins during the course of breast cancers. However, their significance as predictors of 5- year DFS was not achieved in this group of patients. Lymph node invasion was the only independent indicator for recurrent or metastatic breast carcinoma.

Ability of clinical nodal staging to predict histologic nodal status in breast cancer patients.

Axillary lymph node metastasis is the most important prognostic factor for breast cancer. Pathologic examination of axillary lymph node dissection specimens is the gold standard for determining if the tumour has metastasized. Clinical nodal staging may help the physician to plan for management and to decide what advice to give the breast cancer patients. We studied the metastasis predictive ability of clinical lymph node staging, and tried to identify subgroups that were more reliable for clinical staging. Patients and Methods: We did a cross-sectional study by collecting the data of patients who had their breast cancers treated at Siriraj Hospital from 1983 to 1993. The lymph node status from preoperative physical examination was compared to the pathologic result of axillary lymph node dissections. Results: Of 1,355 breast cancer patients, 4 patients were stage 0, 224 were stage I, 891 were stage II, 161 were stage III, and 40 patients were stage IV (with 35 missing). Mean diameter of the cancer was 3.6 cm. The average age at diagnosis was 48.5 years. Fifty one percent (697 patients) had at least one palpable node from preoperative physical examination, and 50% of cases (678 patients) had pathologic axillary lymph node positive for metastasis. When compared to pathologic examination, the accuracy of clinical lymph node staging was 70.6%, with 70% sensitivity and 71% specificity. The accuracy was increased in patients with small (T1) or large primary tumor (T3,4) subgroups. Conclusion: Physical examination of axillary lymph node could be used as a guide for predicting metastasis of breast cancer, but with 25-30% of uncertainty.

Serum and tissue markers in primary breast cancer.

Thirty-three primary breast cancers were analyzed for prognostic markers, Immunohistochemical assay of c-erbB-2 oncoprotein was performed in formalin fixed paraffin-embedded tissue. Enzyme immunoassay and radioreceptor assay for ER and PR were respectively done in tumor cytosol. Pre-opertive blood sample obtained from this group of patients were analyzed for CEA, CA15-3 and MCA levels. About 54% of tumor had c-erbB-2 positive staining. Direct association was observed between tumor size, pathological stage, serum CEA levels and c-erbB-2 expression. No significant association existed between the expression of c-erbB-2 and lymph node invasion, histological type, ER and PR status, serum CA15-3 or MCA levels. Increased incidence of c-erbB-2 overexpression among breast cancer patients with large tumor, more advanced stage and elevated CEA level suggests its value for indicating of greater tumor aggressiveness.

Primary hyperparathyroidism due to parathyriod carcinoma: Report of a case and review of literature.

A 21-year-old male with a history of bone pain for four months is described. He lost 2 cm of his height and also had polyuria and weight loss. Physical examination revealed a cachectic and mildly pale man with a firm mass of 0.8 cm in diameter on the fight side of his neck, generalized muscle wasting and proximal muscle weakness. kyphoscliosis and deformed thoracic cage. Skeletal X-ray showed finding compatible with the changes found in primary hyperparathyroidism. Biochemical parameters revealed a serum corrected total calcium of 15 mg/dl (8.5-10.5 mg/dl), inorganic phosphate of 3.7 mg/dl (305-5.0 mg/dl) and alkaline phosphatase of 1,008 U/l (39-117 U/l). Primary hyperparathyroidism was confirmed by a serum parathyroid hormone level of 1,733 pmol/l (0.100 pmol/l), Ultrasonography and computerized tomography of the neck showed a right neck mass with a diameter of 2 x 2.2 x 3 cm cm which was visualized by 99mTc-sestamibi scan. The patient underwent an uneventful surgical exploration of the neck. Histopathological study of the excised neck mass showed findings consistent with parathyroid carcinoma.

Bloody and serosanguineous nipple discharge.

Spontaneous bloody and serosanguineous nipple discharge is not only a relatively uncommon condition but also an alarming experience for women who suffer it. The objective of this study is to find the underlying causes, clinical pattern and proper management for the individual patient. From 1986 to June 1993 at the Department of Surgery, Siriraj Hospital, 32 cases were identified from the surgical records. All were female who had nonlactational, solitary, unilateral and spontaneous bloody or serosanguineous nipple discharge. Their ages ranged from 16 to 76 years with a mean age of 42 years. 11 of the 32 cases also had an associated definite breast mass and 2 had a subareolar induration. All but one were surgically treated by microdochectomy, segmental resection, excisional biopsy of the mass, and frozen section with mastectomy in 18, 6, 5 and 2 cases respectively. Intraductal papilloma or papillomatosis was the leading underlying cause followed by invasive ductal carcinoma which was found in 9 cases or 28% of the series. The malignant patents tended to be older and almost always had an associated breast mass on physical examination (8 in 9 cases). The risk of malignancy for the associated definite breast mass was statistically significant. Therefore, to eradicate the bleeding and establish a pathological diagnosis, all patients should be treated surgically regardless of the results of investigations. And those who have an associated definite breast mass should be considered to have a malignant growth until proved otherwise.