On the outcome of septoplasty.

In 2019 and 2023, two randomised controlled trials (RCTs) on the effectiveness of septoplasty were published (1,2). Part of the rationale for both studies was that the value of septoplasty had been questioned by policymakers, health insurance carriers and health care providers. The results of both studies showed that patients undergoing septoplasty had a better outcome than patients in the control group. Without questioning these results or the general perception in the rhinology community that septoplasty is of great value to the right patient, we still see the need for caution when interpreting the outcome of the RCTs and when rhinologists try to transfer the results to routine clinical practice. Van Egmond et al. draw the conclusion that the results from their RCT should be applicable to all patients with nasal obstruction due to a deviated septum.

Arm lymphoedema after axillary surgery in women with invasive breast cancer.

BACKGROUND: The primary aim was to compare arm lymphoedema after sentinel lymph node biopsy (SLNB) alone versus axillary lymph node dissection (ALND) in women with node-negative and node-positive breast cancer. The secondary aim was to examine the potential association between self-reported and objectively measured arm lymphoedema. METHODS: Women who had surgery during 1999-2004 for invasive breast cancer in four centres in Sweden were included. The study groups were defined by the axillary procedure performed and the presence of axillary metastases: SLNB alone, ALND without axillary metastases, and ALND with axillary metastases. Before surgery, and 1, 2 and 3 years after operation, arm volume was measured and a questionnaire regarding symptoms of arm lymphoedema was completed. A mixed model was used to determine the adjusted mean difference in arm volume between the study groups, and generalized estimating equations were employed to determine differences in self-reported arm lymphoedema. RESULTS: One hundred and forty women had SLNB alone, 125 had node-negative ALND and 155 node-positive ALND. Women who underwent SLNB had no increase in postoperative arm volume over time, whereas both ALND groups showed a significant increase. The risk of self-reported arm lymphoedema 1, 2 and 3 years after surgery was significantly lower in the SLNB group compared with that in both ALND groups. Three years after surgery there was a significant association between increased arm volume and self-reported symptoms of arm lymphoedema. CONCLUSION: SLNB is associated with a minimal risk of increased arm volume and few symptoms of arm lymphoedema, significantly less than after ALND, regardless of lymph node status.

Phase III development of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire module for women undergoing breast reconstruction.

BACKGROUND: Comprehensive outcome assessments after breast reconstruction (BRR) require surgery-specific patient-reported outcome measures. The aims of this study were to assess the relevance, acceptability and redundancy of questions/items (phase III pretesting) of a new BRR questionnaire evaluating patients' health-related quality of life before and after BRR. Phase III occurred in collaboration with the European Organization for Research and Treatment of Cancer (EORTC) following earlier development phases that identified 31 items. METHODS: The EORTC BRR subgroup applied decision-making rules to each question according to eight EORTC criteria. A total of 197 patients (from the UK, Austria, Belgium, Italy and Sweden) were recruited. Forty-seven patients completed pre- and post-BRR questionnaires prospectively, and 150 reported post-BRR questionnaires only retrospectively. Qualitative debriefing interviews were undertaken in 189 patients. Preliminary psychometric analyses were performed. RESULTS: Thirty-one items fulfilled 'relevance', with none producing 'difficulties'. Ten items were not a priority for 10 per cent of respondents. Of these, two questions concerning muscle twitching in the affected breast and problem with donor-site swelling were deleted. Three redundant items were deleted: weakness in arm, which correlated significantly to the Quality of Life Questionnaire (QLQ) BR23 breast questionnaire, and shape and colour of the affected nipple. Descriptive statistics reduced the module to 26 items conceptualized into three provisional scales (disease treatment/surgery-related symptoms, sexuality and cosmetic outcome) within the newly completed questionnaire, EORTC QLQ-BRR26. CONCLUSION: The QLQ-BRR26 is available for psychometric validation in a large-field international sample. The intended use for QLQ-BRR26 is alongside EORTC QLQ-C30 and QLQ-BR23, in women treated by mastectomy for breast cancer and undergoing all types of BRR.

Mammography casting-type calcification and risk of local recurrence in DCIS: analyses from a randomised study.

BACKGROUND: We studied the association between mammographic calcifications and local recurrence in the ipsilateral breast. METHODS: Case-cohort study within a randomised trial of radiotherapy in breast conservation for ductal cancer in situ of the breast (SweDCIS). We studied mammograms from cases with an ipsilateral breast event (IBE) and from a subcohort randomly sampled at baseline. Lesions were classified as a density without calcifications, architectural distortion, powdery, crushed stone-like or casting-type calcifications. RESULTS: Calcifications representing necrosis were found predominantly in younger women. Women with crushed stone or casting-type microcalcifications had higher histopathological grade and more extensive disease. The relative risk (RR) of a new IBE comparing those with casting-type calcifications to those without calcifications was 2.10 (95% confidence interval (CI) 0.92-4.80). This risk was confined to in situ recurrences; the RR of an IBE associated with casting-type calcifications on the mammogram adjusted for age and disease extent was 16.4 (95% CI 2.20-140). CONCLUSION: Mammographic appearance of ductal carcinoma in situ of the breast is prognostic for the risk of an in situ IBE and may also be an indicator of responsiveness to RT in younger women.

Immediate reconstruction with implants in women with invasive breast cancer does not affect oncological safety in a matched cohort study.

Physicians are still concerned about the oncological safety regarding immediate breast reconstruction (IBR) in breast cancer patients. This study aimed to evaluate possible differences between local, regional, and distant recurrences between women having implant-based reconstruction versus women operated with mastectomy alone. Secondary aims were to evaluate time to oncological treatment as well as disease-free and breast-cancer-specific survival. In a retrospective cohort designed study, 300 reconstructed patients with invasive breast cancer were matched with 300 patients from the population-based Regional Breast Cancer Register of the Stockholm-Gotland health-care region operated with mastectomy alone. They were matched for age, tumor size, nodal stage, and year of operation. Also included were patients treated with neoadjuvant chemotherapy and postoperative radiotherapy. The median follow-up for both the groups was 11.5 years (range 2-20). There were no significant differences in the local recurrence rate, 8.2% in the IBR group and 9.0% in the control group or in the regional recurrence rate, 8.2% versus 9.7%. Distant metastases occurred more frequently in the control group (27.1%) when compared to the IBR group (20.3%). There were no significant differences in time to treatment or in complications rate. Breast cancer mortality was 17% for the IBR group and 23% in the control group during follow-up. This long-term follow-up survey with a well-matched control group demonstrates that IBR with implants is safe to offer patients with invasive breast cancer without any negative effect on the oncological safety.

High satisfaction rate ten years after bilateral prophylactic mastectomy - a longitudinal study.

Women from families with an increased risk for breast/ovarian cancer have undergone bilateral prophylactic mastectomy (BPM) since the early 1990s at the Karolinska University Hospital in Sweden. Perceptions of BPM as reported by the first women who underwent the procedure have previously been evaluated on a short-term basis (1-3 years). The present study aims to evaluate the long-term (10 years) physical and psychological consequences of BPM in the same cohort of women. Some of the very first women to undergo BPM participated in the present interview study (n= 13). The semi-structured interviews focused on the women's long-term experiences related to BPM and immediate breast reconstruction. Overall, the women were satisfied with their decision to undergo BPM and perceived a negligible remaining risk of getting breast cancer. For most women, the operation had not resulted in changes in family life or lifestyle (n= 8), although some described that the relationship with their spouse was affected (8/13), either in a negative (n= 5) or positive (n= 3) way. The cosmetic results were mainly positive (n= 10). Recurrent counselling and support during the whole process of decision, treatment and follow up is recommended.

Impact of preoperative breast MRI on 10-year survival of patients included in the Swedish randomized multicentre POMB trial.

BACKGROUND: The value of preoperative breast MRI as an adjunct technique regarding its effect on re-excision rates has been a subject of discussion. No survival data regarding preoperative breast MRI are available from randomized studies. METHODS: Ten-year follow-up of the POMB randomized multicentre study was analysed, evaluating MRI and its effect on disease-free survival (DFS) and overall survival (OS). Patients with newly diagnosed breast cancer were randomized to either preoperative MRI or conventional imaging. Kaplan-Meier plots were used to analyse DFS and OS, and Cox regression to estimate hazard ratios (HRs). RESULTS: A total of 440 patients, aged 56 years or less, with newly diagnosed breast cancer were randomized to either preoperative MRI (220) or conventional imaging (220; control). Median follow-up for each group was 10 years. DFS rates were 85.5 and 80.0 per cent for the MRI and control groups respectively (P = 0.099). The risk of relapse or death was 46 per cent higher in the control group (HR 1.46, 95 per cent c.i. 0.93 to 2.29). OS rates after 10 years were 90.9 and 88.6 per cent in the MRI and control groups respectively (P = 0.427). The risk of death was 27 per cent higher in the control group (HR 1.27, 0.71 to 2.29). Locoregional, distant, and contralateral recurrence outcomes combined were increased in the control group (P = 0.048). A subgroup analysis of patients with breast cancer stages I-III showed that preoperative MRI improved DFS compared with conventional imaging, but this did not reach statistical significance (P = 0.057). CONCLUSION: After 10 years of follow-up, preoperative breast MRI as an adjunct to conventional imaging resulted in slightly, but non-significantly, improved DFS and OS. Registration number: NCT01859936 (http://www.clinicaltrials.gov).

Parafibromin immunoreactivity: its use as an additional diagnostic marker for parathyroid tumor classification.

Parafibromin is a protein product derived from the hyperparathyroidism 2(HRPT2) tumor suppressor geneand its inactivation has been coupled to familial and sporadic forms of parathyroid malignancy. In this study, we have conducted immunohistochemistry on 33 parathyroid carcinomas (22 unequivocal and 11 equivocal) using four parafibromin antibodies directed to different parts of the protein. Furthermore, for a fraction of cases, the immunohistochemical results were compared with known HRPT2 mutational status. Our findings show that 68% (15 out of 22) of the unequivocal carcinomas exhibited reduced expression of parafibromin while the 25 sporadic adenomas used as controls were entirely positive for parafibromin expression. Additionally, three out of the six carcinomas with known HRPT2 mutations showed reduced expression of parafibromin. Using all four antibodies, comparable results were obtained on the cellular level in individual tumors suggesting that there exists no epitope of choice in parafibromin immunohistochemistry. The results agree with the demonstration of a approximately 60 kDa product preferentially in the nuclear fraction by western blot analysis. We conclude that parafibromin immunohistochemistry could be used as an additional marker for parathyroid tumor classification, where positive samples have low risk of malignancy, whereas samples with reduced expression could be either carcinomas or rare cases of adenomas likely carrying an HRPT2 mutation.

Histopathological risk factors for ipsilateral breast events after breast conserving treatment for ductal carcinoma in situ of the breast--results from the Swedish randomised trial.

AIM: The primary aims were to study risk factors for an ipsilateral breast event (IBE) after sector resection for ductal carcinoma in situ of the breast (DCIS) in a trial comparing adjuvant radiotherapy to no therapy and to assess predictive factors for response to radiotherapy. Secondary aims were to analyse reproducibility of the histopathological evaluation and to estimate correctness of diagnosis in the trial. SETTING: A randomised trial in Sweden (the SweDCIS trial), including 1046 women with a median of 5.2 years of follow-up in a population, offered routine mammographic screening. METHODS: A case-cohort design with a total of 161 cases of IBE (42 of those being members of the subcohort) and 284 sampled for the sub-cohort. Ninety five percent of the participants' slides could be retrieved and were re-evaluated by three experienced pathologists. RESULTS: Low nuclear grade (NG 1-2) and absence of necrosis halves the risk of IBE in both irradiated and non-irradiated patients. Lesion size, margins of excision and age at diagnosis did not modify these associations. The presence of necrosis modified the effect of radiotherapy: relative risk was 0.40 with necrosis present and 0.07 with necrosis absent (p-value for interaction 0.068). In all subsets of prognostic factors, radiotherapy conferred a substantial benefit. The risk factors for in situ and invasive IBE were similar. The agreement between pathologists was moderate (kappa=0.486). Correctness of diagnosis in the subcohort of SweDCIS was 84.8%. CONCLUSION: Although nuclear grade and necrosis carry prognostic information, we could not define a group with very low risk after sector resection alone. Radiotherapy has a protective effect in all substrata of risk factors studied. The interaction between the presence of necrosis and radiotherapy is a clinically and biologically relevant research area.

A screening for BRCA1 mutations in breast and breast-ovarian cancer families from the Stockholm region.

To identify BRCA1 germ-line mutations in the breast and breast-ovarian cancer families in the Stockholm region, a total of 127 families were screened. DNA from 174 patients from these families were studied using various mutation screening techniques, followed by direct DNA sequencing. Mutations were identified in 7 of 20 families with breast and ovarian cancer and in one family with ovarian cancer only, whereas only 1 family of 106 with breast cancer showed a mutation. Thus, germ-line mutations in BRCA1 were found in one-third of the families with both breast and ovarian cancer, but in only 1% of the breast cancer families. The low frequency of germ-line mutations in the site-specific breast cancer families means that other genes are likely to segregate in these families.

Self-perceived, but not objective lymphoedema is associated with decreased long-term health-related quality of life after breast cancer surgery.

BACKGROUND: The primary aim was to compare long-term health-related quality of life (HRQoL) in patients undergoing sentinel lymph node biopsy (SLNB) alone versus axillary lymph node dissection (ALND), with or without axillary metastases. Secondary aims were to a) investigate agreement between objectively measured and self-reported lymphoedema and b) compare, with respect to HRQoL, women with objective arm lymphoedema without subjective ratings and those with no objective but subjective ratings of arm lymphoedema. METHODS: The three study groups were defined by axillary surgery: 1) SLNB alone (N = 140), 2) ALND in patients without axillary metastases (N = 125) and 3) ALND in patients with axillary metastases (N = 155). Preoperatively, one and three years postoperatively arm volume was measured and questionnaires regarding self-perceived symptoms of arm lymphoedema and HRQoL were completed (The Swedish Short Form-36 Health Survey, SF-36). RESULTS: Out of the original 516 who had axillary surgery, 420 (81%) completed the study. There were no statistically significant differences in HRQoL between the three study groups. No statistically significant agreement was found between self-perceived and objectively measured arm lymphoedema. Women without self-perceived arm lymphoedema, regardless of objective arm lymphoedema or not, scored higher on all eight SF-36 domains than those who reported self-perceived arm lymphoedema. CONCLUSION: Women reporting self-perceived arm lymphoedema, regardless of objective lymphoedema or not, have a decreased long-term health-related quality of life. This indicates that more attention should be given to the subjective reports of symptom in order to better help these women.

Alterations of the MEN1 gene in sporadic parathyroid tumors.

Primary hyperparathyroidism is a common endocrine disease that also occurs in a number of inherited disorders, including multiple endocrine neoplasia type 1 (MEN1). Loss of heterozygosity (LOH) in the MEN1 region on chromosome 11q13 has been found in 30% of sporadic parathyroid tumors, making the recently cloned MEN1 gene a prime candidate for involvement in parathyroid tumorigenesis. Using LOH and single strand conformation analysis, we screened 45 sporadic tumors from 40 patients for alterations involving the MEN1 gene. Thirteen tumors showed LOH at 11q13, and in 6 of these cases, somatic mutation of the MEN1 gene was detected. In tumors without LOH, no mutations were detected. The mutations consisted of 3 small deletions, 1 insertion, and 2 missense mutations that had not been reported in MEN1 patients or parathyroid tumors previously. Using messenger ribonucleic acid in situ hybridization, the expression of the MEN1 gene was studied. There was no difference in expression between normal and tumor tissue. In conclusion, the findings of inactivating mutation in tumors with LOH at 11q13 confirm the role of the MEN1 tumor suppressor gene in a subset of sporadic parathyroid tumors.

Alternative genetic pathways in parathyroid tumorigenesis.

In this study 44 parathyroid tumors from 26 sporadic cases, 10 cases previously given irradiation to the neck, and 8 familial cases were screened for sequence copy number alterations by comparative genomic hybridization. In the sporadic adenomas, commonly occurring minimal regions of loss could be defined to chromosome 11 (38%), 15q15-qter (27%), and 1p34-pter (19%), whereas gains preferentially involved 19p13.2-pter (15%) and 7pter-qter (12%). Multiple aberrations were found in sporadic tumors with a somatic mutation and/or loss of heterozygosity of the MEN1 gene. The irradiation-associated tumors also showed multiple comparative genomic hybridization alterations and frequent losses of 11q (50%), and subsequent analysis of the MEN1 gene demonstrated mutations in 4 of 8 cases (50%). The adenomas from familial cases showed few alterations, and in 3 of these tumors a gain of 19p13.2-pter was seen as the only aberration. In this study numerical copy number alterations were frequently detected in sporadic and irradiation-associated parathyroid adenomas, although these tumors are benign. The majority of these alterations were found in tumors with confirmed involvement of the MEN1 gene locus in agreement with a role of the MEN1 gene in genomic stability. Furthermore, the frequent occurrence of MEN1 mutations (50%) in irradiation-associated parathyroid tumors suggests that inactivation of the MEN1 gene is an important genetic alteration involved in the development of parathyroid tumors in postirradiation patients.

Familial isolated hyperparathyroidism maps to the hyperparathyroidism-jaw tumor locus in 1q21-q32 in a subset of families.

Approximately 70 families with familial isolated hyperparathyroidism (FIHP) have been reported. Whether it is a separate entity or a variant of multiple endocrine neoplasia type 1 (MEN1 at 11q13) or hyperparathyroidism-jaw tumor (HPT-JT or HRPT2 at 1q21-32) syndrome is not known. We describe here 3 unreported families with familial primary hyperparathyroidism and evaluate their clinical, pathological, and genetic profiles. Biochemical and radiological screenings for MEN1 were negative for all families. In 2 families with a total of 10 affected cases and 3 female obligate carriers, there is no evidence of jaw or renal lesions despite careful radiological investigations. In both families the disease was linked to the 1q21-q32 region with the maximum logarithm of the odds (lod) scores of 3.10 and 3.43 for markers D1S222 and D1S249 respectively, at recombination fraction of 0. In 1 family 2 types of parathyroid pathology were found: 3 of chief cell type and 1 of oxyphil/oncocytic cell type. Two chief cell tumors and 1 oxyphil tumor were found to have loss of heterozygosity (LOH) involving loss of the wild-type alleles for chromosome 1q markers. In the third family, with 4 affected siblings, a parathyroid carcinoma and 2 cases of polycystic kidney disease were found. The parathyroid carcinoma also showed loss of heterozygosity in the 1q region. In conclusion, we found that the hyperparathyroidism traits in a subset of FIHP families are linked to the 1q21-32 markers in the HRPT2 region. We describe the spectrum of parathyroid disease in 1q-linked families involving 3 different types of pathology and demonstrate for the first time loss of wild-type alleles in these parathyroid tumors. Taken together, the results suggest that some of the FIHP are a variant of HPT-JT and that the gene involved is a tumor suppressor gene.

Preoperative psychological reactions and quality of life among women with an increased risk of breast cancer who are considering a prophylactic mastectomy.

A consecutive sample of 56 women with a familial risk for breast cancer who were considering a prophylactic mastectomy (PM) completed questionnaires preoperatively concerning risk perception, expectations with regard to surgery, anxiety and depressive symptoms (the Hospital Anxiety and Depression Scale (HAD) scale) and quality of life (The Swedish SF-36 Health Survey). 16 had had a previous breast cancer (Group BC) and 40 had not (Group R). They were compared with normative data from an age-matched random sample of the Swedish population and with a reference sample of women with breast cancer. Most women estimated their breast cancer risk accurately. No statistically significant differences were found between Group BC and the normative sample on the HAD scale and SF-36, but Group R reported better physical functioning, emotional role functioning and mental health than the reference sample with breast cancer. Group BC scored closer to them than to the normative sample. Levels of emotional problems and quality of life were comparable to normative values among women considering PM. All women in the present study had previous genetic counselling and our results suggest that their interest in PM was not due to an overestimation of their personal risk.

Histopathological variables and DNA cytometry in parathyroid carcinoma.

To undertake an evaluation of histopathological variables in parathyroid carcinoma, 95 cases with this diagnosis were collected from 37 hospitals. Two tumor categories emerged from a review of tissue sections and follow-up information: 56 cases demonstrating extraglandular invasiveness or tumor recurrence were classified as definitive carcinomas, whereas 39 tumors lacking these criteria were classified as equivocal cases. Several morphological variables other than invasiveness differed between the two groups: Fibrosis, necrosis, nuclear atypia (especially macronucleoli), and mitotic figures were significantly more frequent in the carcinoma group. These variables also showed a positive correlation with an aberrant DNA pattern demonstrated by image cytometry. The triad macronucleoli, more than five mitoses per 50 high-power fields, and necrosis were associated with an aggressive behavior in terms of recurrent disease. A minority of the carcinomas had a bland cytologic appearance and differed from benign lesions only by their invasiveness. Certain patterns of fibrosis and necrosis were common but neither pathognomonic nor constant features of malignancy. Mitotic activity constituted a prognostic risk factor but was of limited diagnostic significance. In half of the carcinomas, the frequency of mitoses did not exceed values recorded in benign parathyroid lesions.

Metastatic parathyroid carcinoma: dilemmas in management.

The incidence of parathyroid carcinoma in patients surgically treated for primary hyperparathyroidism at the University of Michigan Hospital was 0.4% during an 18-year period. The courses of the five patients with metastatic disease are described. Histologic reevaluation and assessment of the DNA ploidy pattern were performed in each case. Localization studies preceded all reexplorations. The number of operative procedures in each patient ranged from two to 10. Two patients are living with recurrent disease and one has been disease free for 42 months. Two patients died after 2 and 12 years, respectively. Three patients had aneuploid tumors; one had a diploid tumor. One patient had both aneuploid and diploid cell populations. Dilemmas in diagnosis, localization, and medical and surgical management were encountered in patients with metastatic carcinoma. The chosen treatment should be evaluated individually in each case because of the variability in aggressiveness of this malignancy. Surgical resection proved most effective in some of these patients for both local and distant recurrences. Bisphosphonates and gallium nitrate have been reported to be effective in controlling hypercalcemia. Only the former had some effect in one of our patients.

Undescended superior parathyroid gland: a potential cause of failed cervical exploration for hyperparathyroidism.

BACKGROUND: The undescended inferior parathyroid gland is a well-established although infrequent embryologic abnormality resulting in an ectopically located gland usually associated with thymic tissue and is found most commonly within the carotid sheath at the level of the carotid bifurcation. Embryologically undescended superior glands (either normal or enlarged), clearly above the level of the upper pole of the thyroid gland and found within or in approximation to the lateral pharyngeal wall, have not been previously described. METHODS: The locations of all parathyroid glands at the time of cervical exploration were carefully examined as to embryologic origin in a combined experience of more than 3000 patients with primary or secondary hyperparathyroidism. RESULTS: Five patients had enlarged abnormal glands located within or in close approximation to the pharyngeal wall. All were above the upper pole of the thyroid gland. Two were identified at reoperation on the basis of localization studies. One gland was found after resection of a massive concomitant cervical goiter. The other two were found after an extensive search for a superior gland. CONCLUSIONS: Undescended superior glands are extremely rare (0.08%). They are located within or in approximation to the pharynx above the level of the thyroid gland with an unusual blood supply, which supports an embryologic rather than acquired cause for their ectopic location.

Decreased expression of calcium-sensing receptor messenger ribonucleic acids in parathyroid adenomas.

BACKGROUND: The set point for parathyroid hormone (PTH) secretion is increased in patients with primary hyperparathyroidism, possibly because of receptor defect(s). A decreased expression of calcium receptor (CaR) messenger ribonucleic acid (mRNA) and protein and a decreased expression of the putative calcium-sensing CAS (gp330/megalin) protein have been demonstrated in parathyroid adenomas. METHODS: Expression of CAS mRNA was studied in matched pairs of adenomas and adenoma-associated biopsy specimens from normal parathyroid glands from 15 patients with sporadic primary hyperparathyroidism. Cryostat sections were hybridized with an oligonucleotide complementary to CAS mRNA, rinsed, air dried, and exposed to x-ray film for semiquantification of radioactivity. RESULTS: Expression of CAS mRNA in the adenomas was lowered significantly to 25% (median; range 9% to 80%) of that of the corresponding biopsy specimens of normal parathyroid glands. No correlation was seen between CAS mRNA in the adenoma and preoperative serum calcium levels, PTH level, or weight of the adenoma. The levels of CAS mRNA were significantly lower than those observed previously for CaR mRNA. There was no significant correlation between the levels of CAS and CaR mRNA. CONCLUSIONS: Lowered levels of receptors sensing extracellular calcium (CaR and CAS) probably contribute to the increased set point for PTH secretion in primary hyperparathyroidism.

Expression of matrix metalloproteinase gelatinase A messenger ribonucleic acid in parathyroid carcinomas.

BACKGROUND: The incidence of parathyroid cancer in patients with hyperparathyroidism is less than 1%. However, these few cases cause diagnostic problems in the absence of clear-cut invasion of adjacent organs or metastasis. New markers are needed to increase diagnostic accuracy. METHODS: Thirty-one parathyroid tumors from patients with primary hyperparathyroidism were collected worldwide. Eighteen tumors were classified as unequivocal cancers, whereas 13 tumors were considered equivocal because of a lack of infiltrative growth or evidence of recurrence. Paraffin sections were hybridized with a 35S-labeled riboprobe complementary to gelatinase A mRNA, dipped in photographic emulsion, developed, counterstained, and then evaluated by light- and dark-field microscopy. RESULTS: Fourteen of the 18 unequivocal parathyroid cancers expressed gelatinase A, as compared with the equivocal tumors, of which only 4 of 13 showed expression. The strongest hybridization signal was seen in stromal cells at the tumor border, most likely fibroblasts and macrophages. No expression was detected in tumor cells. CONCLUSIONS: Invasive growth of many tumors is facilitated by proteolytic enzymes, such as gelatinase A. The presence of gelatinase A mRNA in parathyroid tumors strengthens the suspicion of malignancy but cannot be used as a definitive marker of malignancy.