Absence of progesterone receptor associated with secondary breast cancer in postmenopausal women.

The relationship between expression of receptors for oestrogen and progesterone (ER and PR) and disease progression in breast cancer was investigated by comparing immunocytochemical determinations of ER and PR in fine needle aspirates from primary and secondary breast tumours. Rates of receptor expression were significantly higher in primary than in secondary lesions: for ER 63.3% (n = 689) compared with 45.3% (n = 223), and for PR 53.7% (n = 443) compared with 33.1% (n = 121). The effect of menopausal status was examined by subdividing the patient cohort into those over or under the age of 50 years. In both instances, ER expression in secondary tumours was relatively low; however, only postmenopausal patients had significantly lower rates of PR expression in secondary tumours. Consistent with this, an increase in the ER+PR- profile in secondary tumours compared with primary cases from postmenopausal patients was seen, and in a multivariate analysis, a specific absence of PR expression in secondary tumours was revealed. Comparison of ER and PR expression in simultaneously sampled primary tumours and lymph node metastases from the same patient showed that receptor expression was stable with progression to a metastatic site as results were concordant for ER in 92% (n = 88) and PR in 93.8% of cases (n = 65). These results suggest that absence of PR expression in primary breast cancer is associated with disease progression and may be a marker of an aggressive tumour phenotype.

Simultaneous pancreas and kidney transplant rejection: separate or synchronous events?

The results of simultaneous pancreas and kidney transplantation (SPK) cannot be matched by pancreas transplantation alone (PTA), in part because an independent diagnosis of pancreas graft rejection remains difficult. The relationship between rejection of the pancreas and rejection of the kidney is poorly understood, and it is not known whether simultaneous transplantation of both organs confers true protection to either graft. To study these questions, reliable canine allotransplant models of kidney transplantation alone (KTA), PTA, and SPK were established. Sixty-seven mongrel dogs received KTA (n=21), PTA (n=23), or SPK (n=23) with either no immunosuppression, low-dose cyclosporine (CsA)-based immunosuppression, or high-dose CsA-based immunosuppression. Needle core biopsy (NCB) and fine needle aspiration biopsy (FNAB) were performed at 0, 2, 4, 7, 9, 11, 14, 21, and 30 days or at the time of graft failure. Pancreas and kidney graft survival after SPK was significantly shorter in dogs given low-dose CsA than in dogs given high-dose CsA (pancreas, P<0.04; kidney, P<0.03). Concurrent NCBs and FNABs were performed on 227 occasions in pancreas grafts and 229 occasions in kidney grafts. The time to initial evidence of rejection by NCB was not different in any immunosuppressed group. Synchronous rejection occurred in 73% of immunosuppressed SPK biopsies. Kidney-only rejection occurred in 23% of biopsies and pancreas-only rejection occurred in only 3% after SPK. All markers of pancreas graft rejection were poor, with the most sensitive being NCB of the simultaneously transplanted kidney. In summary, recipients of SPK required more immunosuppression than recipients of PTA, and improved PTA survival should be achievable with more sensitive markers of rejection. Markers of kidney rejection were the most sensitive indicators of pancreas rejection, and independent pancreas rejection was uncommon after SPK.

Percutaneous biopsy of bladder-drained pancreas transplants.

Percutaneous biopsy is a valuable investigation in the management of allograft rejection for all solid organs. Pancreas transplants have not been biopsed percutaneously, though open and percystoscopic biopsies have proved useful. We have compared percutaneous needle core biopsy with fine-needle aspiration cytology for the diagnosis of rejection in 18 patients receiving combined kidney and pancreas transplants and in one who was transplanted with the pancreas alone. Percutaneous needle core biopsy was successful in 37 of 40 attempts (93%), while fine-needle aspiration yielded diagnostic material on 33 of 47 attempts (70%). Transient hyperamylasemia occurred in 29%, returning to baseline in three days. One patient twice developed transient macroscopic hematuria. There was agreement between needle core biopsy and fine-needle aspiration on the diagnosis of rejection on six occasions and for the absence of rejection on 16. There was an 8% false-positive rate for fine-needle aspiration. In 13 instances of histologically proved renal rejection, concurrent pancreas biopsy revealed rejection in 69%. Pancreas rejection was not, however, seen in the absence of renal rejection. In this pilot study, percutaneous biopsy of the bladder-drained pancreas allograft was shown to be a practicable and valuable investigation without major complications.

Percutaneous fine needle aspiration biopsy of canine pancreas allograft provides diagnosis of treatable rejection.

Despite improved pancreas transplant graft survival, early diagnosis of rejection remains a clinical challenge. Using a canine model of whole pancreas transplantation with bladder exocrine drainage we have shown fine needle aspiration biopsy (FNAB) to provide an earlier diagnosis of rejection than fall in urinary amylase (UA). The aim of this study was to assess the ability of anti-rejection therapy to reverse rejection when the diagnosis was based on either FNAB findings or a fall of UA. Sixteen dogs received a total pancreas allograft with an inadequate dose of oral cyclosporine (5 mg/kg/day). Fasting UA levels were measured daily and percutaneous FNAB with ultrasound guidance was performed three times weekly on all dogs. The diagnosis of rejection was made in alternate dogs with either a fall of UA to a level of less than 5000 IU/liter (median 7 days) or when the total corrected increment (TCI) of aspirated infiltrating cells was greater than 2.6 (median 5 days). Anti-rejection therapy consisted of methylprednisolone 10 mg/kg/day iv for 5 days and an increase of oral cyclosporine dosage to 25 mg/kg/day. Early vascular thrombosis (Day 2) occurred in three allografts. Diagnosis of rejection based on a low level of UA permitted the successful reversal of rejection in only one of six grafts, whereas five of seven grafts were successfully treated when rejection diagnosis was based on FNAB. Median allograft survivals were 9 days (range 8-19) and 32 days (range 11-63), respectively (P less than 0.01). The earlier diagnosis of allograft rejection made by FNAB improved the ability of conventional anti-rejection therapy to reverse pancreas allograft rejection and significantly improved allograft survival.

Estrogen receptor immunocytochemical assay on cytologic material from primary and metastatic breast cancer.

The determination of estrogen receptor (ER) status in primary and metastatic breast tumours has been facilitated by the recent advent of monoclonal antibodies to ER. The aim of this study was to determine the feasibility of estrogen receptor immunocytochemical assay (ER-ICA) applied to cytologic specimens from primary and metastatic breast tumours. One hundred and sixty specimens from 133 patients were evaluated by cytologic ER-ICA. Comparison with histologic ER-ICA was available for 28 of the specimens and with cytosol assay for 27 specimens. Some 101 of the 160 samples were breast lesions of which 87 had a definitive diagnosis of breast carcinoma. Of these, 68% were considered positive for ER. Metastatic breast cancers comprised 59 of the 160 specimens of which 37% were found to be positive for ER. The predominant staining intensity (SI) of the nuclei of the tumour cells added to the percentage of cells (PC) stained gave an estrogen receptor score (ERS) in both cytologic and histologic specimens. A positive threshold was determined for an ERS greater than 2, equivalent to ER levels greater than 10 fmol/mg of protein. We observed very good correlation between cytologic ERS and the corresponding cytosol assay values (r = 0.74; p less than 0.001; n = 27). The sensitivity was 95% and the specificity 88%. Correlation with histologic ER-ICA was also very high (r = 0.83; p less than 0.001; n = 28). We assessed the role of video image analysis (VIA) and did not find any additional advantages in evaluating cytologic ER-ICA.(ABSTRACT TRUNCATED AT 250 WORDS)

The value of exfoliative cytology in the diagnosis of oral herpes simplex infection in immunosuppressed patients.

Conventional exfoliative cytology was effective in confirming a clinical suspicion of oral mucosal infection by herpes simplex virus in nineteen out of twenty (95%) immunosuppressed patients who were studied.