High prevalence of MMTV-like env gene sequences in gestational breast cancer.

Gestational breast cancer (BC) is generally associated with rapid growth and increased mortality. Because the presence of MMTV-like sequences in BC has been associated with laminin receptor expression, a marker of poor prognosis, gestational BCs were analyzed for MMTV env gene-like sequences to explore whether MMTV-like sequences were also associated with its adverse outcome. Whereas 30-38% of sporadic BC have the sequences, in gestational BC the prevalence is 62%. We suggest that hormonal response elements present in the MMTV-like LTR may play a role in promoting cell growth, as they do in the mouse system.

Pleomorphic adenoma of the breast. A case report and distinction from mucinous carcinoma.

Pleomorphic adenoma of the breast is a rare, benign tumor accounting for 68 cases in the literature. It is most commonly seen in postmenopausal women and is characterized by an admixture of epithelial and myoepithelial cells embedded in abundant myxomatous stroma. Its clinical and histologic appearance can be challenging and may lead to a misdiagnosis of invasive carcinoma. We report a case of mammary pleomorphic adenoma in an asymptomatic 59-year-old woman and briefly discuss its distinction from mucinous carcinoma through the use of special stains.

Immunohistochemical analysis of prostate specific antigen in breast cancer.

The presence of immunoreactive prostate-specific antigen (IR-PSA) has been reported in breast cancers and has been suggested to confer a positive prognosis. However, recent large, well-controlled studies have found no significant prognostic value when IR-PSA positivity is examined as an independent variable, even when ultrasensitive immunofluorometric techniques are utilized. The present study, using indirect immunohistochemistry on 75 formalin-fixed, paraffin-embedded breast cancers shows PSA immunoreactivity in only seven of 75 cases (9%), suggesting that PSA positivity in breast carcinoma is not useful as a prognostic or tumor marker with hospital-based methods.

Breast cancer in an intramammary sentinel node.

A palpable 3.2 cm infiltrating ductal carcinoma was removed from a 27-year-old woman. Radiologic evaluation of the breasts with mammography and sonography identified an intramammary node between the carcinoma and the axilla. This was localized and removed at the time of axillary dissection. Isosulfan blue, which had been injected into the walls of the lumpectomy cavity to facilitate identification of the sentinel node in the axilla, stained the intramammary node. It contained several foci of carcinoma. Excision of the intramammary nodes may be indicated in breast cancer patients treated with breast conservation.

The significance of malignancies incidental to microcalcifications in breast spot localization biopsy specimens.

BACKGROUND: Incidental breast cancer is occasionally found in spot localization biopsy specimens adjacent to mirocalcifications in benign breast disease. Because this phenomenon could prove problematic for percutaneous sampling of microcalcifications without excisional biopsy, we studied surgical specimens from patients with cancers incidental to microcalcifications and compared them with specimens with microcalcifications within the malignancy. METHODS: The pathology database at the Mount Sinai Medical Center from January 1993 to July 1998 was reviewed to identify breast cancer patients who underwent spot localization biopsy for microcalcifications. Patients presenting with microcalcifications within malignancy (determinate) were compared with patients with mirocalcifications in benign breast tissue adjacent to malignancy (incidental). RESULTS: Thirty-two (13%) of the 241 specimens had microcalcifications in benign tissue adjacent to malignancy and 209 (87%) had microcalcifications within the malignancy. Fifty-six percent of the incidental cases and 65% of the controls had ductal carcinoma in situ. Infiltrating lobular carcinoma accounted for 25% of the incidental cancers and 2% of the determinate cancers (P <0.001). Fifty-seven percent of the infiltrating carcinomas incidental to mammographic findings were infiltrating lobular carcinoma compared with 7% of the nonincidental infiltrating carcinomas. None of the incidental invasive carcinomas were poorly differentiated (P = 0.002). There were no significant differences with regard to age, tumor size, stage, differentiation, estrogen and progesterone receptors, type of surgery and final margin status. In none of the patients with incidental malignancies did local or distant recurrences develop. CONCLUSIONS: Incidental carcinomas were found in 13% of spot localization biopsy specimens obtained for suspicious mammographic microcalcifications and have a favorable prognosis. Infiltrating lobular carcinomas are more commonly found with incidental microcalcifications than with determinate microcalcifications, and incidental invasive carcinomas are less likely to be poorly differentiated. The majority of malignancies, both determinate and incidental to microcalcifications, are due to ductal carcinoma in situ. Incidental malignancies commonly occur adjacent to fibrocystic changes and their other pathologic characteristics are not significantly different from nonincidental carcinomas. Despite the absence of radiographic findings, these patients can be successfully treated with breast conservation.

Invasive micropapillary carcinoma of the breast: eighty cases of an underrecognized entity.

Eighty cases of infiltrating duct carcinoma of the breast with a pure or partial micropapillary component are reported. The cases were analyzed using various parameters, including age at presentation, tumor size, tumor grade, presence of lymphatic invasion, and axillary lymph node status. The patients' age at presentation ranged from 36 to 92 years (mean, 58.8 years). Tumor size ranged from 0.1 to 10 cm (mean, 2.0 cm); 67.5% (54 of 80) were poorly differentiated, and 32.5% (26 of 80) were moderately differentiated; 62.5% (50 of 80) of the cases had lymphatic invasion; 72.3% (47 of 65) of cases with axillary dissections had positive lymph nodes; and 25% (20 of 80) of the tumors were < or = 1.0 cm and 7.5% (6 of 80) were < or = 0.5 cm. The characteristics of these small tumors with an invasive micropapillary component have not previously been reported. Despite their minute size, these small micropapillary carcinomas seem to show the same proclivity for lymphatic spread and nodal dissemination as larger tumors with this unique histologic pattern.

The consequence of undertreating breast cancer in the elderly.

BACKGROUND: Recent studies have noted that a large fraction of elderly patients do not receive conventional treatment for breast cancer. The consequences of undertreatment of the elderly have not been adequately assessed. STUDY DESIGN: The senior author's database (PIT) was used to identify women undergoing potentially curative operations for breast cancer between 1978 and 1998. Risk factors, presentation, pathologic findings, treatment, and outcomes of 206 women aged over 70 years were compared with those of 920 younger patients. In addition, conventionally treated and "undertreated" elderly patients were identified, and their characteristics and outcomes were compared. RESULTS: Older patients' cancers were more often visible on mammography, usually as a mass; younger patients' mammograms were less frequently positive, presenting more often with calcifications (p = 0.002). Cancers of the elderly were better differentiated (p < 0.001) and more likely to be estrogen- and progesterone-receptor positive (p < 0.001; p = 0.007). Patients over 70 had fewer mastectomies (19% versus 33%; p < 0.001) and were also less likely to undergo axillary node dissection (71% versus 81%, p = 0.006), postoperative radiation (69% versus 92%, p < 0.001), and chemotherapy (18% versus 48%, p < 0.001). Fifty-seven percent of older patients were treated with tamoxifen compared with 36% of younger patients (p < 0.001). Elderly patients' rates of local and distant recurrence were comparable to those of younger patients after both mastectomy and breast conservation. Ninety-eight patients (54%) over 70 were undertreated by conventional criteria. Undertreated elderly patients were significantly older (78 versus 76 years, p = 0.003), were diagnosed with excisional biopsy more often (69% versus 57%, p = 0.069) and with fine-needle aspiration less frequently (22% versus 38%, p = 0.069), and were more likely to have breast conservation (90% versus 73%, p = 0.004). Local and distant disease-free survival rates of both groups were comparable. Tamoxifen treatment significantly reduced the chance of developing distant metastasis in node-negative elderly patients with invasive tumors (p = 0.028). Omission of chemotherapy had no impact on disease control in the elderly. Axillary node status and estrogen-receptor status were significantly related to local disease-free survival, and axillary node status was significantly related to distant disease-free survival in multivariate analysis in the elderly. CONCLUSIONS: Elderly breast cancer patients are frequently treated with breast conservation, omitting axillary dissection, radiation therapy, and chemotherapy. Despite undertreatment by conventional criteria, the rates of local recurrence and distant metastasis are not increased in comparison with conventionally treated elderly patients. Tamoxifen should be administered to elderly breast cancer patients with invasive tumors because it significantly improves distant control.

Endometrial cancer in elderly women: A histologic and steroid receptor study.

BACKGROUND: Information on steroid receptor content in endometrial tissue of aging women is limited and somewhat controversial. The high incidence of endometrial cancer (EC) and the implication of hormone replacement therapy (HRT) in this group prompted the investigation of steroid receptors and endometrial cancer histology in the elderly. OBJECTIVE: Review of histologic characteristics correlated with estrogen and progesterone receptors (ER and PR) status in EC in women over 75 years of age in order to determine the prevalence of a more aggressive endometrial neoplasm arising in late postmenopausal atrophic endometrium of elderly patients. METHODS: Histologic slides and deeper sections stained immunohistologically for ER/PR from 54 cases of EC in women aged 75-95 years were reviewed. The histologic characteristics and degree of differentiation were correlated with the steroid receptor status, evaluated on a scale of 0-3. Benign endometrial tissue from women of the same group was used as controls. RESULTS: The 57.4% endometrioid adenocarcinomas were mostly moderately and poorly differentiated. The nonendometrioid carcinomas were anaplastic, papillary, clear cell, squamous cell, mixed müllerian and nongestational choriocarcinoma. The staining intensity for ER/PR decreased with the degree of dedifferentiation being weak or absent in nonendometrioid tumors. CONCLUSION: Elderly patients have less differentiated EC displaying histologically nonendometrioid patterns ('alienation') with no differential loss of receptors in cancer. ER/PR are partly preserved in endometrioid tumors and controls. We conclude that differential loss of receptor capacity is not a factor in pathogenesis of this age-related cancer.

Organochlorine exposures and breast cancer risk in New York City women.

A hospital-based case-control study of breast cancer risk related to organochlorine (OC) exposure was conducted in a multiethnic setting in New York City. We enrolled 175 breast cancer patients and 355 control patients. The overall racial/ethnic distribution was 57% Caucasian, 21% Hispanic, 22% African-American; cases and controls were frequency-matched by age and race/ethnicity. Tumor markers (estrogen and progesterone receptors, p53, erbB-2) were assessed and organochlorines (DDE, DDT, trans-nonachlor, and higher (HPCB) and lower (LPCB) chlorinated biphenyls) were measured in blood serum. Tumors among minority women were of slightly higher stage than among Caucasians, but tumor markers were similar across the racial/ethnic groups. DDE levels were highest among African-American and Hispanic women; DDT was highest among Hispanics; HPCBs were highest among African-Americans; LPCBs were lowest among Hispanics; and trans-nonachlor was highest among African-Americans. However, OC levels were not associated with risk for breast cancer, nor did OCs differ with respect to tumor stage or tumor markers. Higher DDE levels were associated with increasing body mass index (BMI), but with decreasing level of education, frequency of nulliparity, and frequency of family history of breast cancer. HPCB levels decreased with BMI and were not correlated with breast cancer risk factors. These relationships can be attributed to historical patterns of exposure and to metabolic differences in OCs related to BMI.

Subareolar breast cancers.

BACKGROUND: Despite the high rate of pathologic involvement of the nipple-areola complex (NAC) with subareolar cancers and the suboptimal cosmetic results when lumpectomy removes the NAC, breast conservation surgery has been extended to include these patients. METHODS: Ninety-five patients with subareolar cancers operated on between 1979 and 1998 were identified and the relationships between the pathologic findings, treatment, and outcome were studied. RESULTS: Clinical involvement of the NAC (P = 0.001), clinical presentation (P <0.001, mammographic calcium or Paget's disease), and pathologic tumor size (P = 0.019) were significantly related to pathologic involvement of the NAC in univariate analysis. After consideration for clinical NAC involvement, no other variable was significantly related to pathologic NAC involvement in multivariate analysis. Thirty-three patients underwent mastectomy, and 62 were treated with breast conservation. Radiation therapy (P = 0.005), clinical (P = 0.031), and pathologic (P = 0.037) involvement of the NAC were significantly related to local disease-free survival in breast conservation patients in univariate analysis. After consideration for radiation therapy in multivariate analysis, clinical involvement of the NAC was the only additional variable significantly related to local recurrence in breast conservation patients. Clinical or pathologic involvement of the NAC was not significantly associated with local and distant recurrence after mastectomy. No other variable was significantly related to local outcome in univariate analysis in patients treated with mastectomy. CONCLUSIONS: Subareolar cancers can be successfully treated with breast conservation surgery provided adjuvant radiation therapy is always given. Clinical involvement of the nipple-areola complex is associated with high risk of local failure when treated with breast conservation without radiation therapy.

Stage 0 to stage III breast cancer in young women.

BACKGROUND: Breast cancer survival is improving because mammography is leading to diagnosis at earlier stages of the disease. Because young women with breast cancer rarely undergo mammography before diagnosis, outcomes for breast cancer in young women may not be improving. In addition to advanced stage, young age at diagnosis is associated with biologically more aggressive cancers with higher rates of local and distant recurrence. STUDY DESIGN: Risk factors, clinical presentations, pathologic findings, tumor characteristics, extent of disease, treatment, and outcomes for 101 women under age 36 treated for breast cancer between 1989 and 1997 were compared with 631 patients 36 years and older treated by us during the same interval. Stage IV patients were excluded. RESULTS: Patients younger than 36 years were more likely to present with a palpable mass (87% versus 55%, p < 0.001) and were less likely to undergo spot localization breast biopsy for mammographic findings (40% versus 6%, p < 0.001). Patients younger than 36 years had larger tumors (median 2.0 cm versus 1.5 cm, p < 0.001), more nodal involvement (50% versus 37%, p = 0.022), more nodes involved (median 1.0 versus 0, p = 0.010), and were more likely to be diagnosed with stage II or III cancer (60% versus 43%, overall p < 0.001). Young patients' cancers were more poorly differentiated (80% versus 44%, overall p < 0.001), estrogen receptor-negative (52% versus 31%, p < 0.001), aneuploid (70% versus 49%, p = 0.013), and had higher S-phase fractions (59% versus 29%, p = 0.001). Patients less than 36 years were treated more often with mastectomy (59% versus 22%, p < 0.001) and adjuvant chemotherapy (80% versus 54%, p < 0.001) and less often with tamoxifen (36% versus 58%, p = 0.001). Cumulative 5-year local and distant disease-free survival were significantly worse for patients younger than 36 years (p = 0.011 and p = 0.044, respectively). The higher rate of local recurrence in patients less than 36 years was from an excess number of local recurrences in patients treated with breast conservation. After consideration for nodal involvement, chemotherapy, and tamoxifen using the Cox proportional hazards model, no other variable, including age, was significantly related to local disease-free outcomes. After consideration for tumor size and nodal involvement, no other variable was significantly related to distant disease failure rates. CONCLUSIONS: Patients diagnosed with breast cancer before age 36 differ from older patients in numerous respects. They present more often with a palpable mass rather than a mammographic finding and their cancers are more advanced with features that are more aggressive. Despite aggressive treatment, most commonly with mastectomy and chemotherapy, local and distant failure rates are higher than for patients 36 and older. The higher rate of local recurrence in patients less than 36 years reflects an excess number of local recurrences in patients treated with breast conservation.

Lumpectomy margins, reexcision, and local recurrence of breast cancer.

BACKGROUND: The diagnosis of breast cancer is often made by excisional biopsy without margin assessment for mammographic findings or palpable masses. Many patients treated with breast conservation undergo reexcision to obtain clear margins although the relationship between clear margins and local recurrence remains controversial. METHODS: Patients undergoing breast conservation and adjuvant radiation therapy with complete follow-up over 5 years were studied. Factors associated with obtaining clear histopathologic margins and undergoing reexcision to obtain clear margins were studied in relation to the risk of local recurrence. RESULTS: Clear biopsy margins were associated with diagnosis by fine-needle aspiration cytology (fine-needle aspiration 42%, spot localization 11%, excisional biopsy 10%; P <0.001). Reexcision was significantly related to diagnostic method (spot localization 63%, excisional biopsy 36%, fine-needle aspiration 10%; P <0.001), first margin status (clear 0%, close 11%, positive 46%, unknown 48%; P <0.001), patient age (54 years for reexcised patients and 58 for non-reexcised patients; P <0.001), and tumor size (mean tumor size 1. 4 cm for reexcised patients and 1.7 cm for non-reexcised patients; P = 0.003). Patients undergoing reexcision were significantly more likely to be diagnosed by spot localization, have nonnegative excisional biopsy margins, be younger, and have smaller tumors than patients not undergoing reexcision. Local recurrence was not significantly related to margin status (8% with clear margins, 7% with positive margins, 19% with close margins, and 11% with unknown margins) or reexcision (10% local recurrence rate for patients with negative final margins after reexcision and 12% with positive, close or unknown first margin without reexcision). Estrogen receptor status was the only variable related to local recurrence in Cox proportional hazards model (P = 0.009). Estrogen receptor negative patients with nonnegative margins experienced a 20% rate of local recurrence compared with 10% for estrogen receptor negative patients with negative margins and 7% for estrogen receptor positive patients regardless of margin status (P = 0.021). CONCLUSIONS: Clear excision margins are facilitated by preoperative diagnosis by fine-needle cytology. For patients with nonnegative margins, reexcision was more commonly performed in young patients with small tumors diagnosed by spot localization biopsy. The relationship of local recurrence to margins and reexcision was not statistically significant. Estrogen receptor negative tumors with nonnegative margins had a significantly higher rate of local recurrence than estrogen receptor negative tumors with clear margins and estrogen receptor positive tumors regardless of margin status.

Cellular retinol-binding protein expression and breast cancer.

BACKGROUND: The biologic activity of vitamin A depends, in part, on its metabolism to active nuclear receptor ligands, chiefly retinoic acid. The cellular retinol-binding protein (CRBP) binds vitamin A with high affinity and is postulated to regulate its uptake and metabolism. In this report, we analyze the expression of CRBP in normal and malignant breast tissues. METHODS: We evaluated CRBP expression by in situ hybridization in six reduction mammoplasty specimens and 49 human breast carcinoma specimens by use of digoxigenin-labeled RNA probes and in nine cultured mammoplasty specimens by northern or western blot analysis. Statistical significance was evaluated with the chi(2) test or Fisher's exact test if the sample sizes were small. All P values are from two-sided tests. RESULTS: CRBP was expressed in all 15 mammoplasty specimens (normal breast tissue) and in 33 of 35 available specimens of normal tissue adjacent to carcinoma. In contrast, 12 (24%) of 49 carcinoma lesions were uniformly negative for CRBP (P =.023 for comparison with adjacent normal breast tissue). The loss of CRBP expression was as frequent in ductal carcinoma in situ (six [27%] of 22) as in invasive lesions (six [22%] of 27), suggesting that it is a relatively early event in carcinogenesis and not associated with patient age, tumor grade, and expression of steroid receptors or c-Myc. Preliminary experiments did not find an association between CRBP and retinoic acid receptor beta loss, but most (four of five) CRBP-negative tumors were also retinoic acid receptor beta negative. CONCLUSION: CRBP is underexpressed in 24% (95% confidence interval = 12.5%-36.5%) of human breast carcinomas, implying a link between cellular vitamin A homeostasis and breast cancer. We hypothesize that the loss of CRBP restricts the effects of endogenous vitamin A on breast epithelial cells.

Lymphatic invasion, tumor size, and age are independent predictors of axillary lymph node metastases in women with T1 breast cancers.

OBJECTIVE: To identify characteristics of the primary tumor highly associated with lymph node metastases. SUMMARY BACKGROUND DATA: Recent enthusiasm for limiting axillary lymph node dissection (ALND) in women with breast cancer may increase the likelihood that nodal metastases will be missed. Identification of characteristics of primary tumors predictive of lymph node metastases may prompt a more extensive surgical and pathologic search for metastases in patients with negative sentinel lymph nodes or limited ALND. METHODS: The authors studied 850 consecutive patients who underwent ALND for T1 breast cancer. Age, tumor size, histopathologic diagnosis, tumor differentiation, presence of lymphatic invasion, and estrogen and progesterone receptor results were studied prospectively. Stepwise logistic regression was used to identify variables independently associated with axillary lymph node metastases. RESULTS: Lymphatic invasion, tumor size, and age were independently associated with lymph node metastases. Fifty-one percent of the 181 patients with lymphatic invasion had axillary lymph node metastases, compared with 19% of the 669 patients without lymphatic invasion. Thirty-five percent of the 470 patients with tumors >1 cm had nodal involvement compared with 13% of the 380 patients with smaller cancers. Thirty-seven percent of the 63 women younger than age 40 had lymph node involvement compared with 25% of the 787 women older than age 40. Significant correlations were noted between lymphatic invasion and patient age and between lymphatic invasion and tumor size. The proportion of tumors with lymphatic invasion decreased progressively with increasing age and increased with increasing tumor size. CONCLUSIONS: Axillary lymph node metastases are most significantly related to lymphatic invasion in the primary tumor, followed, in order of significance, by tumor size and patient age. Axillary nodal metastases should be suspected in the presence of lymphatic invasion of large tumors in young patients.

Complete removal of nonpalpable breast malignancies with a stereotactic percutaneous vacuum-assisted biopsy instrument.

BACKGROUND: Several devices have been developed for sampling nonpalpable mammographic breast lesions. Complete removal of malignancies with a stereotactic percutaneous directional vacuum-assisted biopsy instrument has been reported. STUDY DESIGN: We reviewed our experience with the percutaneous vacuum-assisted biopsy instrument to identify instances of complete excision of cancers: no residual carcinoma found at surgical excision for malignancies diagnosed by the percutaneous vacuum-assisted biopsy instrument. The radiologic and pathologic characteristics of malignancies completely removed by the percutaneous vacuum-assisted biopsy instrument were compared with those of malignancies with residual carcinoma found at surgical excision. RESULTS: Fifty-two malignancies were diagnosed by the percutaneous vacuum-assisted biopsy instrument: 16 infiltrating ductal carcinomas, 5 infiltrating lobular carcinomas, and 31 ductal carcinomas in situ. No residual carcinoma was found at surgical excision in 9 (17%) of the 52 malignancies. Patients with complete removal of the malignant lesion were younger than patients with incomplete removal (52 versus 58 years; p = 0.069). Completely removed malignancies were smaller on mammography (4 versus 17 mm; p = 0.213), and more specimens were removed (19 versus 15; p = 0.074). All nine completely removed malignancies presented with calcifications without a mass (p = 0.112), and all nine were ductal carcinoma in situ (p = 0.019). CONCLUSIONS: Complete removal of nonpalpable breast malignancies is possible with the stereotactic percutaneous directional vacuum-assisted biopsy device. Complete removal is more likely with removal of a large number of specimens from small areas of mammographic calcifications due to ductal carcinoma in situ.

Mammographic pattern of microcalcifications in the preoperative diagnosis of comedo ductal carcinoma in situ: histopathologic correlation.

OBJECTIVE: The comedo subtype of ductal carcinoma in situ (DCIS) is more aggressive than noncomedo DCIS. Differentiating noncomedo DCIS from the more aggressive comedo subtypes on mammography would allow the surgeon to excise comedo DCIS with a wider margin. The mammographic features of microcalcifications associated with nonpalpable comedo DCIS, noncomedo DCIS and benign disease were compared to determine the usefulness of this finding in diagnosis of comedo DCIS. METHODS: The authors retrospectively and blindly reviewed the mammograms of 91 consecutive patients in whom DCIS was diagnosed by needle localization and surgical excision. An equal number of cases of benign microcalcifications were also reviewed. Microcalcifications were evaluated with respect to pattern, density, configuration and size. These results were correlated with the pathologic findings. RESULTS: All 16 cases (100%) of linear branching calcifications and 34 (80%) of the 43 cases of linear calcifications were associated with comedo DCIS (p < 0.001). The number of calcifications, the density and the size of clustering were not diagnostic of comedo DCIS. Granular calcifications occurred in noncomedo DCIS and in benign disease associated with noncalcifying DCIS. CONCLUSION: Comedo DCIS is suggested by the presence of linear and linear branching microcalcifications on mammography.

CYP17 genotype and breast cancer risk.

The MspAI polymorphism in the 5' untranslated region of CYP17 has been evaluated as a breast cancer risk factor in a hospital-based case-control study in New York City. The study population consisted of 363 women [123 breast cancer patients and 240 patient controls (123 benign breast disease without atypical hyperplasia, 117 women without breast disease)]. There were 224 Caucasians (76 cases, 148 controls), 55 African-Americans (20 cases, 35 controls) and 84 Hispanics (27 cases, 57 controls); 142 premenopausal women and 221 postmenopausal women. Consistent with a previous report (Feigelson et al., Cancer Res., 57: 1063-1065, 1997) we found no evidence to implicate the minor variant (restriction site present allele, designated A2) as a breast cancer risk factor. Furthermore, we sought evidence to implicate the minor variant of CYP17 in the development of more aggressive breast cancers (n = 38/121) as had been reported previously. Although confidence intervals (CI) overlap, the data presented here do not provide support for previously reported findings (odds ratio, 0.9; 95% CI, 0.4-2.0; n = 38 versus odds ratio, 2.5; 95% CI, 1.1-5.2; n = 40). Clearly this question needs to be resolved in a larger study. No evidence was found to support the contention that inheritance of the minor variant is a predictor of early age at menarche. Allelic frequencies between different ethnic groups were not found to be different with the exception of Hispanic controls, in which the genotypic distribution was not consistent with the Hardy-Weinberg equilibrium.

Cytologic findings in the differential diagnosis of C-cell hyperplasia and medullary carcinoma by fine needle aspiration. A case report.

BACKGROUND: The cytologic features of C-cell hyperplasia of the thyroid have not been previously addressed in the literature. We describe the first case, to our knowledge, of C-cell hyperplasia that was suggested by fine needle aspiration. CASE: Cellular material was obtained from a nonnodular region of the thyroid gland in a 67-year-old male with chronic diarrhea, unexplained elevated serum calcitonin, no clinically detectable thyroid mass and no known medical or family history of an endocrine disorder. Aspiration yielded a scant bimodal cell population composed of benign follicular cells and a second population of larger cells, later confirmed as C-cells via immunohistochemistry. Although the diagnosis of medullary carcinoma was entertained, the absence of a discrete mass clinically and the presence of two interspersed, distinct cell populations suggested the alternate diagnosis, C-cell hyperplasia, which was confirmed by subsequent thyroidectomy. CONCLUSION: C-cell hyperplasia can mimic medullary carcinoma biochemically, and this case suggests the possible role of fine needle aspiration of the thyroid to distinguish between the two. In patients with elevated serum calcitonin and absence of a discrete thyroid nodule, the finding of clusters of calcitonin-positive cells intermixed with normal follicular cells by fine needle aspiration may provide a means of making a presurgical diagnosis of C-cell hyperplasia.

Nucleolar localization of BRCA1 protein in human breast cancer.

Both a rabbit polyclonal BRCA1 antibody, K-18, and a mouse monoclonal BRCA1 antibody, AP 16, produced nucleolar epithelial cell staining on frozen tissue sections of human infiltrating mammary carcinomas. There was much less BRCA1 antibody staining in normal tissues; however, 2 intraductal tumors and a papilloma, found in proximity to the carcinomas showed considerable nucleolar immunoreactivity. MCF-7 cells fixed in methanol and immunostained with the same two antibodies also revealed nucleolar staining, however, after 4% paraformaldehyde fixation for three minutes, there were many fewer nuclei stained. Antigen retrieval methods on formalin-fixed, paraffin-embedded specimens produced tumor cell cytoplasmic staining with AP 16 and nuclear staining in both tumor and normal epithelial cells with another BRCA1 monoclonal antibody, SG 11.