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Biomedical subjects

Margaret M Steinhoff

Publications and source records attributed to Margaret M Steinhoff.

At least 19 recordsLinked to original sources

Distribution of GPR30, a seven membrane-spanning estrogen receptor, in primary breast cancer and its association with clinicopathologic determinants of tumor progression.

PURPOSE: The seven transmembrane receptor, GPR30, is linked to estrogen binding and heparan-bound epidermal growth factor release. Here, the significance of GPR30 in human breast cancer was evaluated by comparing its relationship to steroid hormone receptor expression and tumor progression variables. EXPERIMENTAL DESIGN: Immunohistochemical analysis of a National Cancer Institute-sponsored tumor collection comprised of 361 breast carcinomas obtained at first diagnosis (321 invasive and 40 intraductal tumors). Biopsies from 12 reduction mammoplasties served as controls. The distribution pattern of GPR30, estrogen receptor (ER), and progesterone receptor (PR) was correlated with clinicopathologic variables obtained at diagnosis. RESULTS: GPR30, ER, and PR were positive in all 12 normal controls. In contrast, GPR30 expression varied in breast tumors, in which 62% (199 of 321) of invasive tumors and 42% (17 of 40) of intraductal tumors were positive. Codistribution of ER and GPR30 was measured in 43% (139 of 321) of invasive breast tumors, whereas both receptors were lacking (ER-GPR30-) in 19% (61 of 321) of the tumors analyzed, indicating a significant association between ER and GPR30 (P<0.05). The coexpression of PR and ER did not influence GPR30 expression, yet coexpression of GPR30 and ER was linked to PR positivity. Unlike ER, which varied inversely with HER-2/neu and tumor size, GPR30 positively associated with HER-2/neu and tumor size. In addition, GPR30 showed a positive association with metastasis (P=0.014; odds ratio, 1.9). CONCLUSIONS: GPR30 and ER exhibited distinct patterns of association with breast tumor progression variables, including HER-2/neu, tumor size, and metastatic disease. Thus, these results support the hypothesis that GPR30 and ER have an independent influence on estrogen responsiveness in breast carcinoma.

Biomarkers, Tumor↗

Use of X-chromosome inactivation pattern to determine the clonal origins of uterine leiomyoma and leiomyosarcoma.

Uterine leiomyomas (LMs) and leiomyosarcomas (LMSs), both of smooth muscle origin, sometimes coexist in the same uterus. Little genetic evidence exists concerning the developmental relationship between LM and LMS. Using the X-chromosome inactivation pattern of the human androgen receptor gene, we examined the clonality of LM and LMS. Of the 24 patients with LM, 21 had multiple neoplasms; all were clonal and individual LMs derived from separate clones. Of the 20 patients with LMS, 6 exhibited multiple tumors in the uterus, and 4 of these individuals also harbored coexisting uterine LMs. We found all LMSs to be clonal. Separate tumors showed identical pattern of X inactivation in 4 patients, and in 2 other individuals, multiple LMSs developed from independent clones. Among the 4 patients with LMS and coexisting LM, 3 showed the same pattern of X inactivation in LMS and the adjacent LM. In 2 of the 3 patients, the tumor also exhibited a morphological transition between benign cells in LM and malignant cells in LMS, supporting the possibility of transformation from LM to LMS. One patient displayed different clones in LMS and the coexisting LM, indicating their independent origins. We conclude that (i) both LM and LMS are clonal; (ii) different nodules in multiple LM are of independent origins; (iii) multiple lesions of LMS may be either monoclonal or multiclonal; (iv) most LMSs are solitary lesions and are most likely de novo, but an individual LM may undergo "malignant transformation" to a LMS; and (v) some LMSs and coexisting LMs are of independent origins.

Adult↗

Inguinal sentinel node dissection versus standard inguinal node dissection in patients with vulvar cancer: A comparison of the size of metastasis detected in inguinal lymph nodes.

OBJECTIVE: The emergence of sentinel lymph node (SLN) technology has provided the ability for an in depth pathologic evaluation for the detection of metastasis to lymph nodes through the use of ultra-staging. The SLN has been shown to be predictive of the metastatic status of its nodal basin. More recently, SLN dissections have been employed in the evaluation of the inguinal lymphatic basins in patients with vulvar malignancies. We hypothesize that the average size of metastasis detected in non-palpable inguinal lymph nodes is smaller when detected through the use of SLN dissection and ultra-staging versus complete inguinal node dissection (CND). METHODS: This was an IRB approved retrospective study. The tumor registry database was searched to identify all patients diagnosed with a vulvar malignancy from 1990 to 2004. The records were reviewed to identify patients with inguinal lymph node metastasis. Only patients with non-palpable inguinal lymph nodes (metastasis 1 cm or less) were included in the analysis. All pathology slides were reviewed. The smallest metastatic foci of cells were measured from lymph nodes obtained through the traditional complete inguinal lymph node dissection (CND) and compared with the largest metastatic foci of cells detected in sentinel lymph node dissections. The mean size and standard deviation for each group was calculated and analyzed with a Mann-Whitney test. RESULTS: There were 336 inguinal node dissections performed in patients identified with a vulvar malignancy. SLN dissections were performed in 52 groins and CND in 284 groins. Fifty-eight patients were found to have metastatic disease to the inguinal lymph nodes. Thirty of these patients had no evidence of lymph node metastasis on clinical exam or at the time of their EUA. There were 7 groins with metastasis detected through an SLN and 23 groins through a CND. The mean size of the metastatic foci detected in the SLN group was 2.52 mm (SD 1.55) and in the CND group was 4.35 mm (SD 2.63). This was not statistically significant (P = 0.109). However, when comparing the detection of micrometastasis in each set, there was a significant difference (P = 0.02) in the detection of the size of metastasis detected with smaller cluster of cells detected in the SLN group. CONCLUSION: SLN dissection with ultra-staging allows for a more extensive pathologic examination of lymph nodes and may allow for the detection of smaller tumor foci than the traditional pathological examination of lymph nodes obtained from a CND. The clinical implication of the detection of these micrometastasis and smaller metastasis remains to be determined.

Aged↗

Second-trimester maternal serum markers in twin pregnancy with complete mole: report of 2 cases.

We present second-trimester serum marker levels in cases of twin pregnancy with complete hydatidiform mole and a coexistent fetus (CHMCF). Second-trimester inhibin A (InhA) levels have not been previously reported in such cases. Second-trimester maternal serum screening, alpha-fetoprotein (AFP), unconjugated estriol (uE3), human chorionic gonadotropin (hCG), and InhA measurements combined with maternal age to estimate a patient's risk of Down syndrome during pregnancy was performed as a routine prenatal test in 2 cases of CHMCF. Hospital records containing serum marker data, patient history, pathology reports, and pregnancy outcome were reviewed. In cases of CHMCF, maternal serum AFP and uE3 levels were similar to those of a normal singleton pregnancy, whereas hCG and InhA levels were markedly increased. Second-trimester maternal serum marker profiles in cases of CHMCF are a composite of normal singleton and molar tissue secretions. We have found, for the first time, that second-trimester InhA levels are markedly increased in these cases. Serum marker levels may be useful in diagnosis of CHMCF, prenatal counseling, and evaluation of risk for persistent trophoblastic disease.

Adolescent↗

Maspin expression in CIN 3, microinvasive squamous cell carcinoma, and invasive squamous cell carcinoma of the uterine cervix.

Maspin is a serine protease inhibitor with tumor suppression activity. It is expressed in normal breast and prostate tissue but is downregulated or absent in breast and prostate tumors. Recent reports have shown that decreased expression is associated with a greater propensity for metastasis in oral squamous cell carcinomas. We know that some high-grade cervical intraepithelial neoplasia progress to invasive carcinomas while others either persist at the same degree of atypia or regress. The pattern of maspin expression in cervical intraepithelial neoplasia-grade 3, microinvasive squamous carcinomas and overtly invasive squamous cell carcinomas of the uterine cervix was studied to determine the relationship between the extent of maspin expression and the progression of cervical intraepithelial neoplasia to squamous cell carcinoma. In total, 36 cases were evaluated: 18 cases of cervical intraepithelial neoplasia-grade 3, seven cases of microinvasive squamous cell carcinoma and 11 cases of invasive squamous cell carcinoma. A monoclonal antibody was used on paraffin-embedded tissues. Immunoreactivity was scored semiquantitatively using a scale of 0-3. The sums of the scores of the different groups were compared using the Mann-Whitney U-test. A significant decrease in maspin scores was noted between cervical intraepithelial neoplasia-grade 3 vs invasive squamous cell carcinoma (P<0.005), microinvasive squamous cell carcinoma vs invasive squamous cell carcinoma (P<0.05), and cervical intraepithelial neoplasia-grade 3 vs tumor emboli (P<0.005). Although not statistically significant, scores of cervical intraepithelial neoplasia-grade 3 associated with invasive squamous cell carcinoma were lower compared to that cervical intraepithelial neoplasia-grade 3 without invasive squamous cell carcinoma. These findings suggest that maspin likely plays a role in disease progression from in situ to invasive carcinoma. Virtual absence of maspin immunopositivity in tumor emboli indicates that maspin may also play a role in metastasis.

Carcinoma, Squamous Cell↗

HER-2/neu expression in locally advanced breast carcinomas: pre-and post-neoadjuvant chemotherapy.

Clinical studies have shown a correlation of HER-2/neu amplification/over-expression and favorable response to neoadjuvant chemotherapy and anti-HER-2/neu antibody treatment. However, contradictory findings also have been reported. Some tumors may develop resistance to neoadjuvant chemotherapy after an initial period of sensitivity. Our study attempts to evaluate the effects of neoadjuvant chemotherapy on HER-2/neu status in locally advanced breast cancer. Thirty-nine patients with locally advanced breast cancers established by core needle biopsy received neoadjuvant chemotherapy and were compared with 60 patients with breast cancers who did not receive neoadjuvant chemotherapy. IHC for HER-2/neu was performed on paraffin sections of the core biopsy before treatment and the excised specimen following chemotherapy and scored as Negative (0-1+), 2+ and 3+. The results of the study and the controls were compared and analyzed using Fisher's exact test. HER-2/neu IHC scores decreased in 28.5% (15/39) of patients receiving neo-adjuvant chemotherapy compared to 11.7% (7/60) of patients in the control (p < 0.013). HER-2/neu IHC status changed from strongly positive to negative (3+ to 0) in five of 39 (12.5%) in the study group and in 2 of 60 (3.3%) in control group (p = 0.104). For patients receiving neoadjuvant chemotherapy in whom the tumor becomes refractory to chemotherapy or recurs, repeat testing for HER-2/neu status may be necessary. Elimination of HER-2/neu positive tumor cells may account for the changes in the IHC scores and the development of resistance to neoadjuvant chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

ASC:SIL ratio following implementation of the 2001 Bethesda System.

The 2001 Bethesda system (TBS 2001) eliminated the "satisfactory but limited by" category, benign cellular changes (BCC), and the designations "favor benign" (ASC-B) and "favor low grade" (ASC-L) for atypical squamous cells. We compared the unsatisfactory rate and atypical squamous cells:squamous intraepithelial lesions (ASC:SIL) ratio pre- and postimplementation of TBS 2001 to see if there was an increase in unsatisfactory specimens, ASC rate, and altered ASC:SIL ratio. Pap Tests (569,726) reviewed at the Cytopathology Laboratory of Women and Infants Hospital from 1998-2002 were included. TBS 1991 terminology was used through December 31, 2001. Conversion to TBS 2001 took place on January 1, 2002. The average ASC:SIL ratios pre- and postimplementation of TBS 2001 were 1.52:1 and 1.42:1, respectively. The rates of unsatisfactory specimens and ASC remained unchanged. Conversion to TBS 2001 did not adversely affect the ASC:SIL ratio or the detection rates of abnormalities of Pap tests.

Female↗

Incidence of metastasis to the ovaries from nongenital tract primary tumors.

OBJECTIVES: The purpose of this study was to evaluate the characteristics of metastatic tumors to the ovaries in nongenital tract primaries and to determine the route of dissemination. METHODS: An IRB-approved study retrospectively reviewed patient records from January 1992 to January 2003. A tumor registry and pathology database search identified women with metastatic disease to the ovaries that had undergone surgery for the presence of an adnexal mass. The charts were reviewed for age at diagnosis, presenting symptoms, size of ovarian metastasis, laterality of metastasis, and primary tumor site. Pathology reports and specimen slides were reviewed to confirm the diagnosis and evaluate the tumors for various pathological features. RESULTS: A total of 59 cases of metastasis to the ovary were identified. The median age of the study group was 55 years old (range: 27-78). Primary colon cancer was identified in 19 (32.2%) cases; appendix 12 (20.3%); breast 5 (8.4%); small bowel and gastric each contributed 4 (6.8%) cases. Pancreatic cancer added 3 (5.1%), while gallbladder and urinary bladder each contributed 1 (1.7%) case. Tumors of unknown primary contributed 10 (18.5%) of the cases. Stromal invasion was seen in 56 (95%) of the cases and surface involvement in 9 (15%) cases. Bilateral metastasis was found in 39 (66.1%) patients and unilateral metastasis in 20 (33.9%) patients. CONCLUSIONS: Metastatic lesions to the ovary are more commonly seen from primary colon cancer, appendiceal, and breast carcinomas. The mechanism of metastasis is through hematogenous pathways as opposed to a transserosal route.

Adult↗

A randomized trial of the Fischer cone biopsy excisor and loop electrosurgical excision procedure.

OBJECTIVE: To compare specimens obtained with the Fischer cone biopsy excisor or loop electrosurgical excision procedure (LEEP) with respect to number of specimens obtained, margin interpretability, adequacy of excision, and ease of use. METHODS: One hundred eligible patients aged 13 years and older were randomly assigned to treatment with the Fischer cone biopsy excisor or LEEP. Eligibility criteria included: (1) cervical intraepithelial neoplasia (CIN) 2 or 3, (2) persistent CIN 1, or (3) cytologic/histologic discrepancy. Following excision, providers ranked ease of use on a scale of 1 to 10. A pathologist blinded to procedure type analyzed specimens for margin interpretability and adequacy of excision. Before study initiation we calculated that a total of 100 patients would be required to demonstrate a significant difference in the interpretable margin rate of 80% for LEEP and 99% for cone biopsy excisor (power 80%, alpha =.05). RESULTS: After adjustment for ease of use, lesion size, and degree of neoplasia, the cone biopsy excisor was no more likely to result in a single specimen than LEEP (74% versus 63%, relative risk [RR] 0.93, 95% confidence interval [CI] 0.79 -1.11), to result in a specimen with interpretable margins (65% versus 73%, RR 0.97, 95% CI 0.78-1.22), or to result in a fully excised cervical lesion (72% versus 62% for LEEPs, RR 1.08, 95% CI 0.77-1.52). Providers found their experiences with both Fischer cone biopsy excisor and LEEP cone biopsies to be similar, even after adjustment for year of training and previous experience (RR 0.95, 95% CI 0.72-1.24). CONCLUSION: The Fischer cone biopsy excisor and LEEP performed similarly with respect to the number of final specimens, margin interpretability, and ease of use. LEVEL OF EVIDENCE: I

Adolescent↗

Atypical squamous cells, cannot exclude HSIL: a review of original vs. duplicate thin-layer slides.

OBJECTIVE: To assess the utility of consensus review of original ThinPrep slides (Cytyc Corp., Boxborough, Masssachusetts) vs. duplicate slides and to identify the significance of the number of representative cells in classifying atypical squamous metaplastic cells, cannot exclude high grade squamous intraepithelial lesion (ASC-H). STUDY DESIGN: A duplicate ThinPrep slide was prepared from 19 cases of ASC-H. Both original and duplicate slides underwent blinded review by 4 pathologists. Consensus cytologic interpretations (75% agreement) were noted and compared with follow-up diagnoses. Dots with atypical metaplastic cells from each slide were counted and correlated with the consensus cytologic interpretation. RESULTS: Following review of 19 original and 19 duplicate slides, consensus interpretations were reached in 14 and 15 cases, respectively. Nine cases of squamous intraepithelial lesion (SIL) were confirmed by biopsies. Consensus interpretation of original and duplicate slides predicted 7 and 6 cases of SIL, respectively. Consensus interpretation of duplicate slides predicted 60% of histologically benign cases. Two-thirds of nonconsensus cases were histologically benign. Consensus interpretations for high grade SIL were reached more often on slides with greater numbers of atypical squamous metaplastic cells. Fewer abnormal cells were present on the duplicate slides. CONCLUSION: Consensus reviews of original and duplicate slides are equally useful in classifying atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion, but may not be practical in all circumstances. HPV DNA testing of all such cases may better detect clinically significant cases.

Adult↗

Pathologic evaluation of inguinal sentinel lymph nodes in vulvar cancer patients: a comparison of immunohistochemical staining versus ultrastaging with hematoxylin and eosin staining.

OBJECTIVES: To evaluate the value of immunohistochemical (IHC) staining of inguinal sentinel lymph nodes (SLN) found to be negative for metastatic disease by ultrastaging with hematoxylin and eosin (H&E) staining. METHODS: An IRB approved study identified 29 patients who had undergone an inguinal sentinel lymph node dissection for squamous cell carcinoma of the vulva. All sentinel lymph nodes found to be negative for metastatic disease based on ultrastaging with H&E staining were reevaluated with pancytokeratin antibody (AE1/AE3) immunohistochemical (IHC) staining to detect micrometastasis. RESULTS: Twenty-nine patients with squamous cell carcinoma of the vulva underwent an inguinal sentinel node dissection. Nineteen patients had inguinal dissections negative for metastatic disease, 2 patients had bilateral inguinal metastasis, and 8 patients had unilateral inguinal metastasis. A total of 42 groin dissections with SLN biopsies were performed; 12 groins were positive for metastatic disease and 30 were negative based on ultrastaging with eosin and hematoxylin staining. A total of 107 sentinel lymph nodes (2.5 SLN per groin) were obtained, of which 18 SLN contained metastatic disease identified by ultrastaging and staining with H&E. Two SLN contained micrometastasis less than 0.3mm in size and 16 SLN contained metastasis greater than 2mm in size. Eighty-nine SLN found to be negative for metastasis by ultrastaging with H&E staining were also negative for micrometastasis on evaluation with pancytokeratin antibody AE1/AE3 IHC staining. CONCLUSIONS: The addition of immunohistochemical staining to ultrastaging with H&E staining in the pathologic evaluation of inguinal sentinel lymph nodes does not increase the detection of micrometastasis in patients with primary squamous cell carcinoma of the vulva.

Carcinoma, Squamous Cell↗

The effect of neoadjuvant chemotherapy on estrogen and progesterone receptor expression and hormone receptor status in breast cancer.

BACKGROUND: Neoadjuvant chemotherapy may decrease tumor volume to allow breast conservation surgery. Its effect on estrogen and progesterone receptor (ER/PR) expression and hormone receptor (HR) status is controversial. METHODS: From February 2001 to July 2002, 56 breast cancer patients treated with neoadjuvant chemotherapy and 56 non-neoadjuvant therapy (control) patients with adequate tissue samples were identified. Quantitative ER/PR expression was analyzed in preneoadjuvant or preoperative core biopsies and final surgical specimens. Changes between the two groups were compared to determine if alterations were due to neoadjuvant chemotherapy or tissue sampling. RESULTS: The ER/PR expression changed in 34 (61%) neoadjuvant chemotherapy patients and 27 (48%) control patients. These expression changes resulted in HR status (positive/negative) alterations in 3 patients (5%) in both groups. Age, histology, chemotherapy regimen, and neoadjuvant response did not predict change. CONCLUSIONS: Hormone receptor status changed in 5% of neoadjuvant chemotherapy and control groups due to tissue sampling. As these changes may impact treatment, HR expression reanalysis in final surgical specimens is recommended.

Breast Neoplasms↗

A randomized trial of the sleeved cytobrush and the endocervical curette.

OBJECTIVE: To compare endocervical specimens obtained with the endocervical curette to those obtained with the sleeved cytobrush. METHODS: All nonpregnant women undergoing either cervical conization or hysterectomy were eligible for this randomized, split-sample trial. Both endocervical curette and cytobrush sampling were performed on all 62 participants before surgery, with randomization designating the order of the sampling procedures. A pathologist blinded to sampling order reviewed study specimens. The endocervical canals of the surgical specimens were evaluated against endocervical curette and brush samples. Odds ratios (ORs), relative risks (RRs), and risk differences were used to compare the sensitivity and specificity of each procedure in unmatched and matched analyses. RESULTS: There was a significantly higher rate of inadequate specimens in the endocervical curette group (22% versus 2% in the brush group; 95% confidence interval [CI] for the difference: 9%, 31%). Unmatched analysis showed the two tests to be comparable in terms of sensitivity and specificity. Whereas the specificities of both tests were high (100% for the endocervical curette, 88% for the brush; RR 1.13, 95% CI 1.00, 1.28), the sensitivities were poor (44% for the sleeved brush and 32% for the endocervical curette; RR 1.38, 95% CI 0.65, 2.94). Matched analysis showed the sleeved endocervical brush to be a more sensitive sampling method compared with the curette (OR 2.04, 95% CI 0.98, 4.22). Sparse data prevented a matched analysis on the specificity of the two tests. CONCLUSION: Endocervical sampling with the sleeved cytobrush achieves similar sensitivity and specificity to that of traditional endocervical curettage. Given the much greater rate of inadequate specimens when using the endocervical curette, the sleeved cytobrush is a reasonable alternative to this technique.

Adult↗

Sentinel node identification and the ability to detect metastatic tumor to inguinal lymph nodes in squamous cell cancer of the vulva.

OBJECTIVES: The goal of this study was to identify one or more inguinal sentinel nodes in patients with primary squamous cell carcinoma of the vulva and to determine the ability of the sentinel node to predict metastasis to the inguinal lymphatic basin. METHODS: Techniques employing technetium-99m (Tc-99m) sulfur colloid and isosulfan blue dye were utilized to identify sentinel nodes in the inguinal lymphatic beds. Technetium-99m sulfur colloid was injected intradermally at the tumor margins 90-180 min preoperatively followed by a similar injection of isosulfan blue dye 5-10 min before the groin dissection. A handheld collimated gamma counter was employed to identify Tc-99m-labeled sentinel nodes. Lymphatic tracts that had taken up blue dye and their corresponding sentinel node were also identified and retrieved. A completion inguinal dissection was then performed. Each sentinel node was labeled as hot and blue, hot and nonblue, or cold and blue. The sentinel nodes were subjected to pathologic examination with step sections and nonsentinel nodes were evaluated in the standard fashion. RESULTS: Twenty-one patients with a median age of 79 were entered onto protocol and a total of 31 inguinal node dissections were performed. A sentinel node was identified in 31/31 (100%) groin dissections with the use of Tc-99m. Isosulfan blue dye identified a sentinel node in 19/31 (61%) groin dissections. Surgical staging revealed 7 patients with stage I disease, 5 with stage II disease, 5 with stage III disease, and 4 with stage IV disease. Lymph nodes in 9 groin dissections were found to have metastatic disease, and in 4 of these dissections, the sentinel node was the only positive node. Lymph nodes in 22 groin dissections had no evidence of metastasis. No false-negative sentinel lymph nodes were obtained (sentinel node negative and a nonsentinel node positive). CONCLUSION: Tc-99m sulfur colloid is superior to isosulfan blue dye in the detection of sentinel nodes in inguinal dissections of patients with vulvar cancer. A sentinel node dissection utilizing Tc-99m alone can identify a sentinel node in all inguinal dissections. Pathologic examination with step sections has shown the sentinel node to be an accurate predictor of metastatic disease to the inguinal nodal chain.

Carcinoma, Squamous Cell↗

Vulvar epithelioid sarcoma in pregnancy.

BACKGROUND: Epithelioid sarcoma is a soft tissue tumor rarely found centrally and even less commonly on the vulva. Vulvar sarcoma in pregnancy is also exceedingly rare with only five cases reported to date, none of which have been an epithelioid sarcoma. CASE: We report a case of a 29-year-old woman presenting with a vulvar epithelioid sarcoma at 36 weeks of gestation. The patient underwent a radical resection 6 weeks postpartum followed by chemotherapy. Despite a radical hemivulvectomy and doxorubicin and ifosfamide chemotherapy, she developed pulmonary metastasis and died of tumor-related pulmonary failure secondary to her disease 612 months after diagnosis. To our knowledge this is the first case of a vulvar epithelioid sarcoma presenting during pregnancy. The English literature is reviewed and a total of 18 previous cases of vulvar epithelioid sarcoma have been reported outside of pregnancy. Insight into the biological behavior and therapeutic management of this disease is discussed. CONCLUSION: The optimal management of vulvar epithelioid sarcoma remains to be determined. However, it would seem that early and aggressive surgical resection provides the best possibility for cure. The role of radiation and/or chemotherapy remains to be determined.

Adult↗

Clinical axillary recurrence in breast cancer patients after a negative sentinel node biopsy.

BACKGROUND: The purpose of this study was to determine the axillary recurrence rate in breast cancer patients with a negative sentinel lymph node who did not have an axillary node dissection. METHODS: Sentinel lymphadenectomy for breast cancer patients, without axillary node dissection if the node was negative, was introduced in 1998 at our institution. This study includes those women with a negative sentinel lymph node. Adjuvant chemotherapy was administered based on primary tumor characteristics. If breast radiotherapy was used, no attempt was made to include the axilla. RESULTS: From January 1998 to December 2001, 206 patients (208 breast cancers) had a negative sentinel lymph node. The median age at diagnosis was 56 years and median tumor size was 1.2 cm. With a median follow-up of 26 months, there have been 3 axillary recurrences with a clinical sentinel lymph node false negative rate of 1.4%. CONCLUSIONS: In this study, the clinical false negative rate of a sentinel lymph node biopsy is 1.4%. Our study provides further evidence supporting the use of sentinel lymphadenectomy in women with breast cancer.

Adult↗

Axillary staging using ultrasound-guided fine needle aspiration biopsy in locally advanced breast cancer.

BACKGROUND: Axillary lymph node status is important for staging and planning therapy prior to neoadjuvant chemotherapy in patients with locally advanced breast cancers (LABC). The objective of this study was to evaluate the use of axillary ultrasonography coupled with fine needle aspiration biopsy (US-FNAB) to determine lymph node status prior to initiation of neoadjuvant chemotherapy. METHODS: Patients with a LABC, defined as a breast cancer clinically larger than 3.0 cm or a cytology positive axillary lymph node, were evaluated by clinical examination followed by ultrasonographic evaluation. Lymph nodes were categorized as suspicious for malignancy based on size >1.0 cm, decrease in the fatty hilum, or parenchymal echogenicity. US-FNAB was performed on all patients. Most patients received neoadjuvant chemotherapy followed by definitive surgery. Axillary surgery consisted of axillary lymph node dissection. Axillary status by clinical examination and US-FNAB was compared with that obtained by axillary node dissection. RESULTS: From January 1998 to May 2001, 26 patients (27 axillae) presented with LABC to our institution. The median age of these patients was 48 years. The sensitivity and specificity of US-FNAB for evaluating axillary metastatic disease in patients with LABC were 100% and 100%, respectively. CONCLUSIONS: In patients with locally advanced breast cancer, axillary ultrasonography coupled with fine needle aspiration biopsy can accurately stage the axilla. It is particularly useful and should be used more frequently in patients undergoing neoadjuvant chemotherapy. The use of ultrasonography to stage the axilla in patients who present with small breast cancers should be explored.

Adenocarcinoma↗

Expression of cyclin D1 in normal, metaplastic, hyperplastic endometrium and endometrioid carcinoma suggests a role in endometrial carcinogenesis.

CONTEXT: Endometrioid carcinoma is often preceded by characteristic histopathologic lesions known as endometrial hyperplasia. Estrogen appears to be involved in the development of endometrioid carcinoma. Other mechanisms of endometrial carcinogenesis include mutations in p53 and PTEN tumor suppressor genes and overexpression of cyclin D1. However, the pattern of cyclin D1 expression is not well defined in normal, hyperplastic, neoplastic, and metaplastic endometrium. DESIGN: Cyclin D1 immunohistochemical analysis was used to evaluate 108 fixed, paraffin-embedded endometrial biopsy specimens and uterine resections obtained from 108 patients. Specimens included proliferative and secretory endometria, simple and complex hyperplastic lesions, and endometrioid adenocarcinoma. Normal and metaplastic surface epithelia were also evaluated independently of glandular morphologic features. RESULTS: Cyclin D1 was significantly overexpressed in glands with complex hyperplasia and endometrioid adenocarcinoma compared with proliferative or secretory endometrium and simple hyperplasia. Significant overexpression was also noted in papillary, syncytial, and squamous metaplasias compared with normal surface epithelium or epithelium with tubal metaplasia. CONCLUSION: Overexpression of cyclin D1 increases from normal endometrium to hyperplasia and carcinoma, suggesting that it may play a role in endometrial carcinogenesis. Overexpression of cyclin D1 in endometrial glands was independent from overexpression of cyclin D1 in surface metaplastic epithelium.

Carcinoma, Endometrioid↗