Immunohistochemistry as a predictor of clinical outcome in patients given postoperative radiation for subtotally resected pituitary adenomas

Summary There is general agreement that postoperative radiation therapy is beneficial for patients with subtotally resected pituitary adenomas. We have identified 41 such patients treated during a 20-year period who received postoperative irradiation for a pituitary adenoma. The usual dose was 5040 cGy in 28 fractions. The mean follow-up time was 10.3 years. On routine hematoxylin and eosin (H&E) staining, there were thirty-three chromophobe, seven eosinophilic, and one basophilic adenoma. Tissue blocks were stained for growth hormone (GH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), prolactin (PRL), and/or adrenocorticotropin ACTH) using the peroxidase-antiperoxidase immunohistochemistry (IHC) method. Routine H&E staining was a poor predictor of the IHC stain. While most patients with a known clinical endocrine syndrome stained positive on IHC for the suspected offending hormone, many patients without a clinical syndrome also stained positive indicating the presence of hormonally occult adenomas in this locally invasive group. The IHC stain results were compared to clinical outcome. The presence of positive GH IHC staining decreased the 15-year progression-free survival (PFS) from 100% to 64% compared to GH negative adenomas (p=0.06). There was a trend toward decreased 15-year PFS in patients who did not stain for LH. Positive staining for prolactin, ACTH, or TSH had no influence on the progression-free survival. We conclude that additional prognostic information can be obtained in this subset of patients (by performing IHC analysis) that is not known by the clinical presentation or appearance on H&E stain.Supported by the American Cancer Society Clinical Oncology Career Development Award.     

Pituitary adenomas in old Sprague-Dawley rats: a histologic, ultrastructural, and immunocytochemical study

Fifty-five adenomas were identified and characterized in the anterior pituitaries of 27 male and 39 female SD rats, over 24 months of age, by histology, ultrastructural morphology, and immunocytochemistry. Adenomas were found in 85% of male and 79% of female rats; all known adenohypophysial hormones were represented in various tumors. Prolactin (PRL)-containing adenomas were the most common (47.2%); luteinizing hormone-(LH)-containing adenomas (16.3%), immunonegative adenomas (12.7%), PRL- and growth hormone (GH)-containing adenomas (10.9%), thyroid-stimulating hormone (TSH)-containing adenomas (3.6%), adrenocorticotropin hormone (ACTH)-containing adenomas (3.6%), and GH-containing adenomas (1.8%) were also identified. Unexpected combinations were observed in 3 tumors (5.4%); a GH-LH-containing adenoma, a PRL-ACTH-containing adenoma, and a PRL-LH-TSH-containing adenoma were noted. One intermediate lobe adenoma and 1 metastatic plasmacytoma were diagnosed. It can be concluded that spontaneous pituitary adenomas in aging SD rats are potential models of the human disease because of diversity of hormone content and morphologic appearance.     

Immunohistochemical detection of human Natural Killer cell like immuno-reactivity in human pituitary adenomas,using monoclonal antibody NK-1

Natural killer (NK) cells are specialized lymphocytes which arecharacterized as non-T and non-B cells, as they lack classic T and B cellsurface markers. Recently, NK like immunoreactivity has been identified inendocrine and neuronal tissues as well as in the tumors derived from theneuroectoderm and neuroendocrine system. We examined the expression of NK-1like immunoreactivity in 6 normal pituitary glands and in 55 cases ofneoplastic pituitaries (16 growth hormone (GH) producing adenomas, 14prolactin (PRL) producing adenomas, 4 thyrotropin (TSH) producing adenomas,5 adrenocortocitropin (ACTH) producing adenomas and 16 non-functioningadenomas) immunohistochemically. The expression of the S-100 protein, whichis a marker for folliclo-stellate (FS) cells, which have been reported tosecrete cytokines as immuno-endocrine modulators, were also examined. Innormal pituitary glands, NK-1 was detected in all 6 tissues in the cytoplasmof about 5–10% of the anterior pituitary cells. By serialsectioning and double immunostaining, NK-1 immunopositivity was frequentlyfound to be localized in ACTH cells. The colocalization with other anteriorpituitary hormones such as GH, PRL, the beta-subunit of luteinizing hormone(LH), follicle stimulating hormone (FSH), TSH and-subunit of glycoprotein (SU) was not observed. The S-100immunopositive FS cells, which were scattered among hormone producing cells,were closely associated with NK-1 immunoreactive cells in the normalpituitaries. Among the 55 cases of pituitary adenomas, NK-1 was present inall the types of pituitary tumors, and a total of 33 (60.0%)contained NK-1 positive tumor cells. The frequency of NK-1 immunoreactivityin the individual adenoma types was; 14 of 16 GH producing adenomas(87.5%), 7 of 14 PRL producing adenomas (50%), 3 of 4 TSHproducing adenomas (75%), 3 of 5 ACTH producing adenomas(60%), and 5 of 16 nonfuctioning adenomas (31.3%). By doubleimmunostaining, NK-1 was found to be frequently colocalized with ACTH inACTH producing adenomas, and was colocalized with PRL in PRL producingadenomas, or with GH, PRL or the -subunit in GH producing adenomacells. NK-1 immunoreactive cells were observed in close association withS-100 immunopositive FS cells in the adenomas. Our results may indicate thatNK-1 positive cells may have functions as a paracrine modulators of theirneighboring cells, which includes S-100 positive FS cells.     

乳腺癌与乳腺增生病某些内分泌激素的差异及其临床意义

目的通过比较乳腺癌与乳腺增生病患者内分泌激素变化,对内分泌激素与免疫系统的关系进行初步分析. 方法随机选取绝经前和绝经后的乳腺癌患者各28例、乳腺增生病患者各22例,在治疗前采血样,对垂体激素6项（PRL、GH、TSH、ACTH、FSH、LH）和性类固醇激素3项（E2、P、T）进行检测,采用秩和检验,正态近似法（Wilcoxon法）对结果行统计学分析. 结果绝经前乳腺癌患者FSH 水平高于乳腺增生患者,其它垂体激素（PRL,GH,TSH,ACTH,LH ）和性类固醇激素（E2,T,P）水平无显著性差异（P〉0.05）.绝经后乳腺癌患者ACTH水平高于乳腺增生病患者,其它垂体激素（PRL,GH,TSH,FSH, LH）和性类固醇激素（E2,T, P） 比较含量无显著差异（P〉0.05）.结论绝经前乳腺癌患者血浆中的FSH和绝经后乳腺癌患者ACTH水平高于乳腺增生病患者,说明乳腺癌患者内分泌激素与免疫系统之间正常规律被打破.下丘脑-垂体-肾上腺轴（HPA）短、长反馈失调,使免疫功能受抑制;雌激素诱导癌细胞基因突变,雄激素刺激细胞的敏感性增加,加速乳腺癌的发展.     

垂体腺瘤术后免疫组化分型与术前激素水平相关性研究

目的:回顾性分析垂体腺瘤手术患者病理免疫组化染色结果与术前相关激素水平的相关性。方法:收集自2011年1月至2016年12月在青岛大学附属医院行手术治疗的垂体腺瘤患者189例,术前行影像学检查、垂体相关激素测定,术后行病理免疫组化染色。采用SPSS 17.0软件进行统计学分析,采用双变量相关分析中的Spearman分析判断两种变量之间的关联性,通过Kappa值判断术前激素水平与病理诊断的一致性。P＜0.05差异有统计学意义。结果:189例垂体腺瘤患者,＞40~60岁组构成比明显高于≤20岁、＞20~40岁、＞60~80岁各组（60.8% vs 1.1%、22.8%、15.3%,均P＜0.05）;大腺瘤明显多于微腺瘤和巨大腺瘤（86.5% vs 4.7%、8.8%,P＜0.05）;PRL瘤血清PRL程度与肿瘤直径呈正相关（r=0.530,P＜0.05）。GH瘤血清GH水平与肿瘤直径呈正相关（r=0.629,P＜0.05）,与年龄呈负相关（r=-0.715,P＜0.05）;垂体PRL瘤、GH瘤血清学诊断与术后免疫组化染色诊断的符合率分别为85.5%、78.9%,Kappa系数分别为0.688、0.465,说明两种诊断的一致性好;以PRL＞100 ng/mL作为PRL瘤的血清学诊断标准时,其与免疫组化染色诊断的符合率和Kappa系数最高,为81.9%和0.517。结论:手术的垂体腺瘤中以大腺瘤为主,好发年龄＞40~60岁。血清PRL、GH水平均与肿瘤直径呈正相关;GH水平与年龄呈负相关。垂体腺瘤临床血清学诊断与病理免疫组化诊断有一致性,以PRL瘤、GH瘤的一致性为最高。PRL＞100 ng/mL可以作为诊断PRL瘤的血清学参考值。     

血清性激素水平及癌基因c-erbB-2在胃癌中的表达及临床意义

目的 :探讨胃癌患者血清性激素水平及癌组织中c erbB 2基因表达的临床意义。方法 :采用放射免疫法 ,测定 67例胃癌患者血清黄体生成素 (LH ) ,卵泡刺激素 (FSH) ,催乳素 (PRL) ,睾酮 (T )及雌二醇 (E )水平 ,同时检测癌组织中c erbB 2基因表达。结果 :胃癌患者LH、FSH、PRL水平均高于对照组 ,P >0 0 5 ,T、E2 水平低于对照组。其中 ,男性胃癌患者血清T水平显著低于对照组 ,P <0 0 5 ,与胃癌浸润深度 (P <0 0 5 )、肿瘤大小 (P <0 0 5 )、淋巴结转移 (P <0 0 5 )密切相关 ;胃癌组织中 ,c erbB 2基因表达阳性率为 3 7 3 1% (2 5 /67) ,与胃癌浸润深度(P <0 0 5 )、淋巴结转移 (P <0 0 5 )密切相关 ,与肿瘤大小无关。结论 :男性血清T水平及c erbB 2基因与胃癌生长、浸润、转移有密切关系 ,可作为判断预后的独立指标。     

绝经后乳腺癌雌、孕激素受体状态与血清性激素水平的关系

目的探讨绝经后乳腺癌雌激素受体(ER)、孕激素受体(PR)状态与患者血清性激素水平的关系及意义。方法使用全自动免疫分析仪化学发光分析法检测41例乳腺癌患者血清性激素六项(LH、FSH、PRL、E2、P、T)水平,免疫组化EnVision二步法检测乳腺癌ER、PR表达状态。结果绝经后乳腺癌PR阴性组与PR阳性组比较,患者血清LH、FSH水平显著增高(P值分别为0.005和0.031),PRL、E2、P、T水平在二组间差异无统计学意义;在ER阴性组与ER阳性组之间所测性激素水平差异无统计学意义。结论绝经后乳腺癌PR表达状态可能与垂体激素LH、FSH水平有关。     

胃癌、大肠癌患者血清性激素水平测定的临床意义

目的：探讨胃肠癌患者血清性激素水平及其临床意义。方法：采用放射免疫法，测定116例胃肠癌患者血清黄体生成素（LH），卵泡刺激素（FSH），催乳素（PRL），睾酮（T）及雌二醇（E2）水平。结果：胃癌患者LH，FSH，PRL水平均高于对照组（P＞0．05），T，E2水平均低于对照组，男性胃癌患者T水平显著低于对照组（P＜0．05），年龄小于60岁的男性胃癌患者血清T水平随肿瘤恶性程度的增加而明显下降（P＜0．01），结直肠癌患者TH，FSH，PRL，T水平与正常人比较，无显著性差异（P＞0．05），男性患者血清E2水平在正常值范围，女性患者E2水平显著低于正常人（P＜0．05），并在绝经期前随肿瘤恶性程度的增加而明显下降（P＜0．01），结论：男性胃癌患者血清T水平和女性结直肠癌患者血清E2水平，可作为判断患者病情的指标之一。     

Neuroendocrine effects of subcutaneous interleukin-2 injection in cancer patients

Intravenous interleukin-2 (IL-2) administration has been shown to influence several hormonal secretions. The present study was carried out to investigate the endocrine effects of subcutaneous therapy with IL-2. Six patients with advanced renal cancer were studied. They were treated subcutaneously with IL-2 according to the schedule proposed by Atzpodien et al. Venous blood samples were collected at O-time and 1, 8 and 12 hours after the first IL-2 pulse of 9 X 10(6) IU/m2 at 8.00 a.m.; on a separate occasion, samples were collected during a saline infusion only. In each blood sample, serum levels of cortisol, beta-endorphin, GH, PRL, FSH, LH, TSH and the pineal hormone melatonin were measured by RIA. Both cortisol and beta-endorphin significantly increased after IL-2 injection. GH rose but not to a significant extent. PRL, FSH, LH and TSH did not change after IL-2. Finally, melatonin levels markedly decreased after IL-2 injection in the only 2 patients with elevated concentrations of this hormone before the start of immunotherapy. These results suggest that the endocrine effects of subcutaneous IL-2 therapy are similar to those previously described with intravenous administration.     

Endocrine and clinical effects of an LHRH analogue in pretreated advanced breast cancer

Buserelin represents one of the main LHRH analogues. It appears to be effective in untreated metastatic breast cancer, whereas its activity in pretreated advanced patients remains to be established. To evaluate endocrine and clinical effects of buserelin in pretreated advanced mammary carcinoma, 14 postmenopausal women with metastatic breast cancer, which had been previously treated with hormones and/or chemotherapy, entered the study. Buserelin was subcutaneously injected at a daily dose of 1.5 mg for 7 days, then intranasally at a daily dose of 1.2 mg until progression. Before and after the 7 days of subcutaneous administration of the LHRH analogue, FSH, LH, estradiol, testosterone basal serum levels, and PRL response to TRH were examined. After the 7 days of buserelin subcutaneous injection, a significant decrease in FSH, LH and estradiol values was observed, whereas testosterone was not affected. PRL response to TRH did not change after buserelin subcutaneous treatment in 8 patients, it decreased in one and was completely abolished in the last 5 cases. All patients whose PRL response to TRH did not decrease had a progression within the first month of therapy, whereas only 1 of 6 patients whose PRL response to TRH was reduced or abolished following buserelin administration showed a progression. Among the other 5 cases, 2 minor responses and 3 stable diseases were achieved. These preliminary results suggest that buserelin has only a limited effectiveness in metastatic breast cancer patients who have been previously treated with hormones and/or chemotherapy, and that its activity in the control of tumor growth is associated with a reduction in PRL secretion.     

9例无功能性胰岛细胞瘤TSH、FSH和LH的异位表达

目的检查多种糖蛋白激素在无功能性胰岛细胞瘤组织中的分布，并探讨肿瘤组织发生学。方法对９例无功能性胰岛细胞瘤进行促甲状腺素（ＴＳＨ）、促卵泡成熟激素（ＦＳＨ）和促黄体素（ＬＨ）等糖蛋白激素及６种胰腺的肽类激素免疫组织化学标记。结果９例肿瘤中ＴＳＨ阳性３例（３３％）；ＦＳＨ阳性５例（５６％）；ＬＨ阳性２例（２２％）。另外，胰岛素阳性４例（４４％）；胰高血糖素阳性６例（６７％）；生长抑素阳性６例（６７％）；胰多肽弱阳性１例。其中１种糖蛋白激素阳性３例，２种激素阳性２例，３种糖蛋白激素阳性１例。多数肿瘤同时存在糖蛋白激素和肽类激素阳性细胞。结论这类肿瘤不仅能合成或分泌肽类激素，也能异位产生糖蛋白激素。     

Prospective hormone study of hypothalamic-pituitary function in patients with nasopharyngeal carcinoma after high dose irradiation

With the aim of evaluating the effect of high dose irradiation (6,500 cGy/36 fractions or higher) to pituitary fossa, a prospective study was carried out in patients with nasopharyngeal cancer by a serial determination of several hormones in the serum, before and after the course of radiation therapy (RT). The radiation treatment field was at least 1 cm above the skull base with bilateral parallel opposing fields. Hormone assays were performed three times on each patient: (1) prior to, (2) one month after, (3) 15-18 months after radiation therapy. The study included determination of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), cortisol, growth hormone (GH) and prolactin concentrations and LH-releasing hormone, thyrotrophin-releasing hormone stimulation and insulin tolerance tests were also carried out. Complete profiles were obtained in 24 patients (16 males and 8 females), aged 16-67 years. The results showed a significant decrease in the level of serum peak value of LH in males 18 months after therapy, and also in GH both one month and 18 months after therapy. A significant increase in the peak value of serum TSH observed after therapy. Decreased serum FSH, cortisol and prolactin levels were noted, but these did not reach statistical significance. The decrease in GH level appeared earlier and was more sensitive than that found for the other hormones, and could prove to be a useful parameter for clinical evaluation. None of the patients showed any clinically recognizable symptoms or signs of hormone deficiency in the 18-33 months following completion of the radiation therapy.     

人垂体腺瘤细胞原代培养的纯化

背景与目的：较纯的人垂体腺瘤细胞对垂体腺瘤的生物学特性、病因、发病机制等的研究非常重要，本文探讨原代培养垂体腺瘤的细胞纯化方法。方法：采用三种原代培养方法对垂体腺瘤细胞进行培养，方法Ⅰ为目前常用的垂体瘤细胞培养方法，方法Ⅱ结合使用右旋颉氨酸（D-valine）替代左旋颉氨酸（L-valine）的DMEM D-valine培养液，方法Ⅲ采用反复贴壁法结合DMEM D-valine培养液培养。观察其细胞形态变化和生长特征。免疫组织化学染色法检测培养细胞生长激素（growth hormone，GH）、泌乳素（prolactin，PRL）的表达。结果：3种方法均能成功培养出垂体腺瘤细胞，呈圆形或椭圆形，其纯度随培养时间的延长逐渐下降，培养第20天其平均纯度分别为40％、46％、96％。方法Ⅲ明显高于方法Ⅰ和方法Ⅱ，差异具有显著性意义（P〈0．01）：腺瘤细胞分别呈GH、PRL阳性表达，成纤维细胞表达Ⅰ型胶原。结论：反复贴壁法结合DMEM D-valine培养液培养法可得到纯度达95％以上的人垂体腺瘤细胞，纯化后的细胞可分别呈GH和PRL阳性表达，为进一步研究人垂体腺瘤的发病机理、药物治疗和颅外移植等方面奠定了实验基础。     

An immunohistochemical study of the incidence and significance of human gonadotrophin and prolactin binding sites in normal and neoplastic human ovarian tissue

An immunoperoxidase technique has been utilised for the demonstration of follicle stimulating hormone (FSH), luteinising hormone (LH) and prolactin (PRL) binding sites in normal human ovaries and in a wide range of benign and malignant epithelial tumours of the ovary. The incidence of FSH, LH and PRL binding was, respectively, 32%, 41% and 39% in normal ovaries, 30%, 18.5% and 22.5% in benign epithelial tumours and 51%, 32% and 43% in malignant epithelial neoplasms. The incidence of FSH binding was significantly higher in malignant epithelial neoplasms than in either normal ovaries or benign epithelial tumours but otherwise no correlation was found between hormone binding capacity and the degree of malignancy of epithelial ovarian tumours, the histological type of the tumour, the degree of differentiation of the malignant epithelial tumours or the presence or absence of metastatic disease. Well differentiated malignant tumours did, however, tend to stain more strongly than did poorly differentiated neoplasms, thus suggesting that the number of binding sites per cell tends to decrease with decreasing degrees of differentiation.     

Prolactin and pituitary gonadotropin values and responses to acute luteinizing hormone-releasing hormone (LHRH) challenge in patients having long-term treatment with a depot LHRH analogue.

Sixty patients with advanced prostatic carcinoma were treated with monthly subcutaneous injections of a depot formulation of goserelin, a luteinizing hormone-releasing hormone (LHRH) analogue (Zoladex, ICI Pharma, Destelbergen, Belgium). All patients were regularly evaluated with measurements of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and prolactin (PRL) levels. In 15 patients among them who could be treated for more than 42 months, an LHRH stimulation test was performed at the end of each 28-day period and before the next administration of the depot formulation. A complete and maintained suppression of both T and LH levels was seen. FSH levels also decreased, but to a lesser extent than LH levels, and showed a small escape after reaching a minimum value after 1 month of therapy. The LHRH challenge after 42 months of therapy elicited no significant responses of LH and FSH levels. The PRL values showed a small decrease.     

Intrasellar gangliocytomas associated with acromegaly

The present study was designed to investigate the immunohistochemical characteristics of gangliocytomas associated with growth hormone (GH)-secreting pituitary adenomas. In our surgical collection of 476 GH-secreting adenoma cases, we examined tumor tissue from 6 patients (1.3%). All 6 patients were women, ranging from 29 to 52 years (mean, 40.3±9.5 SD) of age. Among 470 patients with GH-secreting adenomas without gangliocytoma, there were 255 female and 215 male patients. The preponderance of female patients with gangliocytomas was striking. Histological examination of the resected specimens showed areas of ganglion cells and adenomatous cells. Ganglion cell lesions were stained positively for synaptophysin (4 of 4; 100%) and neurofilament (4 of 4; 100%) as well as GH-releasing hormone (5 of 6; 83.3%). Subtypes of GH cell adenomas included 4 cases of sparsely granulated type and 2 cases of mixed GH and prolactin (PRL) cell adenomas. Based on these findings, we hypothesized that the intrasellar gangliocytoma promoted the growth of the pituitary adenoma by chronic overstimulation from excess GH-releasing hormone.     

Pituitary-ovarian function in breast cancer patients on adjuvant chemoimmunotherapy.

One hundred thirty-one patients with operable breast cancer were treated with adjuvant chemoimmunotherapy consisting of 5-fluorouracil, adriamycin, cyclophosphamide, and BCG (FAC-BCG). Fifty-five of 131 patients were premenopausal of which 71% (38/55) became amenorrheic. To determine the mechanism of amenorrhea, we measured the immunoreactive serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and plasma estradiol (E2) before and after intravenous administration of luteinizing hormone-releasing hormone (LH-RH) in 11 unselected premenopausal patients who developed amenorrhea and 11 unselected patients who did not. Serum prolactin (PRL) levels were also measured before and after iv administration of thyrotropin-releasing hormone (TRH). Our results showed that patients who developed amenorrhea had abnormally high serum LH and FSH levels at basal and after LH-RH stimulation and low plasma estradiol. Serum PRL levels were normal. Patients who developed amenorrhea were older than those who did not, but their serum LH and FSH levels were also significantly higher and plasma estrogens were significantly lower than that found in 11 normal women with regular menses of the same age range. These results indicate that amenorrhea that develops in some patients with breast cancer after FAC-BCG therapy is a result of primary ovarian failure.     

大剂量甲地孕酮治疗晚期乳腺癌的内分泌激素改变

目的：了解大剂量甲地孕酮治疗晚期乳腺癌后体内内分泌激素水平改变可能存在的临床意义。方法：选择女性晚期乳腺癌病例共24例以大剂量甲地孕酮（HDMA）治疗（1200mg/d);并测定治疗前后尿17－羟类固醇和17－酮类固醇和血清LH、FSH、E2、PRL、TSH和孕酮（P）水平。结果：LH和FSH降低有显统计意义;E2升高一倍,但没有统计学意义,而PRL升高则有显统计学意义;孕酮轻微下降和TSH轻微升高,无统计意义;24小时尿17－羟类固醇和17－酮类固醇排出量显增加。结论：HDMA可能是通过下丘脑－垂体－肾上腺（性腺）轴的负反馈抑制作用,使LH和FSH分泌下降;体内E2和PRL升高尽管未见与HDMA的临床疗效有确切相关性,但其高泌乳素和高雌激素水平可能对患的预后不利。     

A preliminary study of serum concentrations of soluble epidermal growth factor receptor (sErbB1), gonadotropins, and steroid hormones in healthy men and women.

Soluble ErbB (sErbB) growth factor receptors are being investigated as cancer biomarkers. Gonadotropic and steroid hormones have been shown to modulate the expression of ERBB family members in vivo. Accordingly, the range of sErbB1 values and their relationship to gonadotropic and steroid hormones need to be established in healthy subjects to provide a baseline for future clinical studies. We assayed sera from healthy men and women to determine p110 sErbB1 concentrations by acridinium-linked immunosorbent assay (ALISA). Follicle-stimulating hormone (FSH), estradiol, and testosterone concentrations were measured using the ACS:180 Immunoassay Analyzer. Luteinizing hormone (LH) and progesterone concentrations were quantified using the Access Immunoassay System. Unadjusted for age, p110 sErbB1 concentrations in healthy men and women do not differ significantly. However, sErbB1 concentrations show a strong age-gender interaction, increasing with age in men but decreasing with age in women. Consequently, sErbB1 concentrations are significantly higher in premenopausal women compared with either postmenopausal women or age-matched men and in age-matched men compared with postmenopausal women. Serum sErbB1 concentrations show significant negative associations with both FSH and LH concentrations in healthy women and a significant positive association with FSH concentrations in healthy men. Univariate linear regression models show that these respective gonadotropic hormones and age are independent predictors of sErbB1 concentrations in men and women. Multivariate models show that when age and FSH and LH concentrations are mutually adjusted for each other, they account for 22% of the variability observed in sErbB1 concentrations in healthy women. These data support the hypothesis that gonadotropic and steroid hormones may modulate ERBB1 expression in vivo and suggest that age- and gonadotropin-adjusted sErbB1 concentrations may be of clinical utility. Furthermore, these data demonstrate that gender, age, menstrual cycle phase, menopausal status, and exogenous hormone use must be considered when using serum p110 sErbB1 concentrations as cancer biomarkers.