垂体腺瘤术后病理免疫组化分型与术前血清激素水平的相关性

doi:10.3877/cma.j.issn.2095-9141.2025.05.006

目的

探讨功能性垂体腺瘤（PAs）术后病理免疫组化分型与术前血清激素水平的相关性。

方法

回顾性选取宁夏医科大学总医院神经外科自2015年7月至2020年11月行手术治疗的PAs患者作为研究对象。按照术前病理免疫组化染色分类指南将PAs分为促肾上腺皮质激素（ACTH）瘤、泌乳素（PRL）瘤、促性腺激素（GnH）瘤[黄体生成素（LH）瘤与卵泡刺激素（FSH）瘤]、生长激素（GH）瘤、促甲状腺激素（TSH）瘤及零细胞腺瘤。收集患者的一般资料、术前血清中激素值、术前影像学检查报告及术后病理免疫组化染色结果。采用Spearman相关分析评估术前激素水平与年龄、性别及肿瘤大小等变量的相关性；采用Kappa一致性检验评估术前激素水平与术后免疫组化分型的诊断一致性。

结果

213例PAs患者中，41~60岁组的人数最多（P<0.05）；大腺瘤构成比明显高于微腺瘤和巨大腺瘤（P<0.05）。GH瘤中术前GH水平与年龄呈中度负相关（r=-0.703，P<0.05）；在多激素腺瘤中术前PRL与性别有关（r=0.400，P<0.05），术前FSH水平与年龄有关（r=0.427，P<0.05），所有术前激素水平与肿瘤大小均无相关性（P>0.05）。不同术前血清PRL水平分层中，以PRL>100 ng/mL作为诊断参考指标时一致率和Kappa系数最高（94.05%，0.589），而在多激素腺瘤、零细胞腺瘤、ACTH瘤、GH瘤、TSH瘤和GnH瘤中术后病理免疫组化染色诊断与术前激素水平的一致性均欠佳。

结论

术前血清激素水平与术后免疫组化分型之间的相关性具有显著的肿瘤类型特异性。PRL瘤的临床血清学诊断与病理免疫组化诊断具有一致性，且PRL>100 ng/mL可以作为诊断PRL瘤的血清学参考值；而多激素腺瘤、零细胞腺瘤、ACTH瘤、GH瘤、TSH瘤和GnH瘤中的术后病理免疫组化染色诊断与术前激素水平不一致。

关键词: 垂体腺瘤, 激素水平, 病理免疫组化, 一致性

Objective

To investigate the correlation between postoperative pathological immunohistochemical classification of pituitary adenomas (PAs) and preoperative serum hormone levels.

Methods

Patients with PAs who underwent surgical treatment in Neurosurgery Department of General Hospital of Ningxia Medical University from July 2015 to November 2020 were selected as the study subjects. According to the preoperative pathological immunohistochemical staining classification guidelines, PAs were classified into adrenocorticotropic hormone (ACTH) tumors, prolactin (PRL) tumors, gonadotropin (GnH) tumors [luteinizing hormone (LH) tumors and follicle stimulating hormone (FSH) tumors], growth hormone (GH) tumors, thyroid stimulating hormone (TSH) tumors, and zero cell adenomas. General patient data, preoperative serum hormone levels, preoperative imaging reports, and postoperative pathological immunohistochemical staining results were collected. Spearman correlation analysis was used to assess the relationship between preoperative hormone levels and continuous variables such as age, gender, and tumor size. The Kappa consistency test was used to evaluate the diagnostic agreement between preoperative hormone levels and postoperative immunohistochemical classification.

Results

Among the 213 patients with PAs, the 40-60 years age group had the highest number of cases (P<0.05); The proportion of macroadenomas was significantly higher than that of microadenomas and giant adenomas (P<0.05). In GH-secreting adenomas, preoperative GH levels showed a moderate negative correlation with age (r=-0.703, P<0.05). In multihormonal adenomas, preoperative PRL levels were correlated with gender (r=0.400, P<0.05), preoperative FSH levels were correlated with age (r=0.427, P<0.05), and there is no correlation between preoperative hormone levels and tumor size (P>0.05). Among different preoperative serum PRL level stratifications, using PRL>100 ng/mL as the diagnostic reference index yielded the highest agreement rate and Kappa coefficient (94.05%, 0.589). However, the consistency between postoperative pathological immunohistochemical staining diagnosis and preoperative hormone levels was poor in multi hormone adenomas, zero cell adenomas, ACTH tumors, GH tumors, TSH tumors, and GnH tumors.

Conclusions

The correlation between preoperative serum hormone levels and postoperative immunohistochemical classification has significant tumor type specificity. The clinical serological diagnosis of PRL-secreting adenomas was consistent with pathological immunohistochemical diagnosis, and PRL>100 ng/mL could serve as a serological reference value for diagnosing PRL-secreting adenomas. However, the postoperative pathological immunohistochemical staining diagnosis is inconsistent with preoperative hormone levels in multi hormone adenomas, zero cell adenomas, ACTH tumors, GH tumors, TSH tumors, and GnH tumors.

Key words: Pituitary adenomas, Hormone level, Pathological immunohistochemistry, Concordance

表1 不同年龄段垂体腺瘤患者性别构成[例（%）]

Tab.1 Gender composition of pituitary adenoma patients in different age groups [n(%)]

年龄分组	例数	男性（n=115）	女性（n=98）	χ²值	P值
≤20岁组	2（0.94）	2（100.00）	0	-	-
21~40岁组	45（21.13）^a	26（57.78）^a	19（42.22）^a	1.089	1.089
41~60岁组	123（57.75）^ab	64（52.03）^ab	59（47.97）^ab	0.203	0.203
61~80岁组	43（20.19）^ac	23（53.49）^ac	20（46.51）^ac	0.209	0.209
χ²值	143.920	68.417	76.449
P值	<0.001	<0.001	<0.001

表1 不同年龄段垂体腺瘤患者性别构成[例（%）]

Tab.1 Gender composition of pituitary adenoma patients in different age groups [n(%)]

年龄分组	例数	男性（n=115）	女性（n=98）	χ²值	P值
≤20岁组	2（0.94）	2（100.00）	0	-	-
21~40岁组	45（21.13）^a	26（57.78）^a	19（42.22）^a	1.089	1.089
41~60岁组	123（57.75）^ab	64（52.03）^ab	59（47.97）^ab	0.203	0.203
61~80岁组	43（20.19）^ac	23（53.49）^ac	20（46.51）^ac	0.209	0.209
χ²值	143.920	68.417	76.449
P值	<0.001	<0.001	<0.001

表2 不同分型的垂体腺瘤术前相关激素水平与年龄、性别及肿瘤大小的相关性

Tab.2 Correlation of preoperative relevant hormone levels with age, gender and tumor size in different subtypes of pituitary adenomas

分型	性别		年龄		肿瘤大小
分型	r值	P值	r值	P值	r值	P值
ACTH瘤	-0.182	0.296	-0.052	0.767	-0.337	0.047
GH瘤	0.325	0.203	-0.703	0.002	-0.103	0.693
PRL瘤	-0.268	0.298	0.217	0.402	0.275	0.286
GnH瘤	0	1.000	0.311	0.241	0.119	0.660

表2 不同分型的垂体腺瘤术前相关激素水平与年龄、性别及肿瘤大小的相关性

Tab.2 Correlation of preoperative relevant hormone levels with age, gender and tumor size in different subtypes of pituitary adenomas

分型	性别		年龄		肿瘤大小
分型	r值	P值	r值	P值	r值	P值
ACTH瘤	-0.182	0.296	-0.052	0.767	-0.337	0.047
GH瘤	0.325	0.203	-0.703	0.002	-0.103	0.693
PRL瘤	-0.268	0.298	0.217	0.402	0.275	0.286
GnH瘤	0	1.000	0.311	0.241	0.119	0.660

表3 69例多激素腺瘤患者术前激素水平与年龄、性别及肿瘤大小的相关性

Tab.3 Correlation of different preoperative hormone levels with age, gender and tumor size in 69 patients with polyhormonal adenomas

激素类型	性别		年龄		肿瘤大小
激素类型	r值	P值	r值	P值	r值	P值
ACTH	-0.030	0.820	0.010	0.939	0.220	0.091
GH	0.067	0.613	-0.227	0.081	-0.016	0.902
TSH	0.220	0.091	-0.085	0.520	-0.077	0.557
PRL	0.400	0.002	-0.110	0.403	0.110	0.401
FSH	0.306	0.018	0.427	0.001	-0.101	0.441
LH	0.299	0.020	0.276	0.033	-0.230	0.077

表3 69例多激素腺瘤患者术前激素水平与年龄、性别及肿瘤大小的相关性

Tab.3 Correlation of different preoperative hormone levels with age, gender and tumor size in 69 patients with polyhormonal adenomas

激素类型	性别		年龄		肿瘤大小
激素类型	r值	P值	r值	P值	r值	P值
ACTH	-0.030	0.820	0.010	0.939	0.220	0.091
GH	0.067	0.613	-0.227	0.081	-0.016	0.902
TSH	0.220	0.091	-0.085	0.520	-0.077	0.557
PRL	0.400	0.002	-0.110	0.403	0.110	0.401
FSH	0.306	0.018	0.427	0.001	-0.101	0.441
LH	0.299	0.020	0.276	0.033	-0.230	0.077

表4 术前激素水平与年龄、性别及肿瘤大小的相关性

Tab.4 Correlation of preoperative hormone levels with age, gender and tumor size

激素类型	性别		年龄		肿瘤大小
激素类型	r值	P值	r值	P值	r值	P值
ACTH	-0.152	0.362	-0.081	0.627	-0.189	0.256
GH	0.142	0.394	-0.257	0.119	-0.079	0.636
TSH	0.007	0.965	0.081	0.627	0.134	0.424
PRL	0.328	<0.001	0.017	0.821	0.051	0.487
FSH	0.169	0.022	0.299	<0.001	-0.091	0.217
LH	0.103	0.164	0.193	0.009	-0.175	0.017

表4 术前激素水平与年龄、性别及肿瘤大小的相关性

Tab.4 Correlation of preoperative hormone levels with age, gender and tumor size

激素类型	性别		年龄		肿瘤大小
激素类型	r值	P值	r值	P值	r值	P值
ACTH	-0.152	0.362	-0.081	0.627	-0.189	0.256
GH	0.142	0.394	-0.257	0.119	-0.079	0.636
TSH	0.007	0.965	0.081	0.627	0.134	0.424
PRL	0.328	<0.001	0.017	0.821	0.051	0.487
FSH	0.169	0.022	0.299	<0.001	-0.091	0.217
LH	0.103	0.164	0.193	0.009	-0.175	0.017

表5 不同病理分型术前激素水平与病理免疫组化染色结果的一致性分析

Tab.5 Analysis of the consistency between preoperative hormone levels and pathological immunohistochemical staining results in different pathological stagings

分型	术前激素水平	免疫组化		一致率（%）	P值	Kappa系数
分型	术前激素水平	阳性	阴性	一致率（%）	P值	Kappa系数
多激素腺瘤	至少2种激素升高	32/69	37/144	74.05	<0.001	0.364
零细胞腺瘤	5种激素均没升高	28/44	16/169	66.49	0.001	0.229
ACTH瘤	ACTH升高	6/40	9/173	79.46	0.084	0.118
GnH瘤	FSH或LH升高	10/18	17/195	88.11	<0.001	0.386
GH瘤	GH升高	11/20	9/193	80.00	0.001	0.229
PRL瘤	PRL>53.1 ng/mL	13/20	16/193	89.19	<0.001	0.465
	PRL>100 ng/mL	11/20	9/193	94.05	<0.001	0.589
	PRL>150 ng/mL	9/20	10/193	94.04	<0.001	0.563
	PRL>200 ng/mL	8/20	1/193	93.51	<0.001	0.507

表5 不同病理分型术前激素水平与病理免疫组化染色结果的一致性分析

Tab.5 Analysis of the consistency between preoperative hormone levels and pathological immunohistochemical staining results in different pathological stagings

分型	术前激素水平	免疫组化		一致率（%）	P值	Kappa系数
分型	术前激素水平	阳性	阴性	一致率（%）	P值	Kappa系数
多激素腺瘤	至少2种激素升高	32/69	37/144	74.05	<0.001	0.364
零细胞腺瘤	5种激素均没升高	28/44	16/169	66.49	0.001	0.229
ACTH瘤	ACTH升高	6/40	9/173	79.46	0.084	0.118
GnH瘤	FSH或LH升高	10/18	17/195	88.11	<0.001	0.386
GH瘤	GH升高	11/20	9/193	80.00	0.001	0.229
PRL瘤	PRL>53.1 ng/mL	13/20	16/193	89.19	<0.001	0.465
	PRL>100 ng/mL	11/20	9/193	94.05	<0.001	0.589
	PRL>150 ng/mL	9/20	10/193	94.04	<0.001	0.563
	PRL>200 ng/mL	8/20	1/193	93.51	<0.001	0.507

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Correlation between immunohistochemical typing of postoperative pathology and preoperative serum hormone levels in pituitary adenomas

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Correlation between immunohistochemical typing of postoperative pathology and preoperative serum hormone levels in pituitary adenomas