Endometrial carcinoma, types 1 vs type 2

It is important to differentiated types 1 and 2 endometrial carcinoma, since they have different prognostic and therapeutic implications. In difficult cases, a combination of ER, MIB1, p53 may be helpful.

	Type 1	Type 2
prototypic form	endometrioid carcinoma	uterine (papillary) serous carcinoma
typical patient	perimenopausal or early postmenopausal women	elderly women
	background of endometrial hyperplasia	background of atrophic endometrium
	low-grade	high-grade
	oestrogen-dependent	not oestrogen-dependent
	may show a focal or diffuse papillary pattern	a glandular variant shows little or no papillary formation but has high-grade cytology
oestrogen receptor	usually positive; high grade cases may be negative	negative
MIB1 proliferation index	low	high
p53	negative; high grade cases may be positive	diffuse positivity
b-catenin	8/17 in grade III endometrioid carcinoma4	0/174
E-cadherin	1/17 in grade III endometrioid carcinoma4	7/174

One study⁵ established criteria, then applied them to problematic cases:

	Reference 5	typical uterine serous carcinoma	FIGO grade II endometrial endometrioid carcinoma	diagnostically challenging uterine serous carcinoma (tubular/glandular architecture without prominent papillae initially diagnosed as EEC, but with high grade cytology and/or metastasis as USC)
	p53 over-expression (all positive cases showed staining of at least 75% of tumour nuclei)	14/16 (one case showed complete negativity, one case weak staining of less than 25% of nuclei)	1/13 (five cases showed weak focal staining)	6/8 (two cases were completely negative: one case was heterogeneous)
	b-catenin (all positive cases showed cytoplasmic/nuclear staining of less than 25% of tumour cells)	0/16	9/13	1/8
	Cyclin-D1 (most positive cases were focal)	3/16	7/13	0/8
	ER (positive cases usually showed staining of more than 75% of tumour nuclei)	5/16	11/12	3/8
	PR	2/16	12/13 (greater than 75% of nuclei in 9 cases)	3/8
	PTEN loss (scored positive if more than 90% loss of staining)	0/16	8/13	1/8
				On discriminant analysis, 6 of 8 cases were confidently diagnosed as serous
	On multivariate analysis, lack of p53 over-expression, PR positivity and loss of PTEN were most predictive of endometrioid carcinomas.

This study also showed the variation in immunophenotype in subtypes of endometrial carcinoma⁶:

		Endometrioid carcinoma		Serous carcinoma	Clear cell carcinoma	Carcinosarcoma (epithelial component)
		FIGO grade 1 and 2	FIGO grade 3
	p16	3/42	10/40	22/24	5/11	6/9
	ER	31/37	20/40	13/24	1/11	2/9
	PR	35/42	16/38	13/24	5/11	1/9
	mCEA	3/42	1/40	3/24	2/11	0/9
	Vimentin	38/42	30/37	19/23	10/11	9/9

References

¹ McCluggage, W. G. (2004). "A critical appraisal of the value of immunohistochemistry in diagnosis of uterine neoplasms." Adv Anat Pathol 11(3): 162-71.

² McCluggage, W. G. (2002). "Recent advances in immunohistochemistry in gynaecological pathology." Histopathology 40(4): 309-26.

³ Wheeler, D. T., K. A. Bell, et al. (2000). "Minimal uterine serous carcinoma: diagnosis and clinicopathologic correlation." Am J Surg Pathol 24(6): 797-806.

⁴ Schlosshauer, P. W., L. H. Ellenson, et al. (2002). "Beta-catenin and E-cadherin expression patterns in high-grade endometrial carcinoma are associated with histological subtype." Mod Pathol 15(10): 1032-7.

⁵ Darvishian, F., A. J. Hummer, et al. (2004). "Serous endometrial cancers that mimic endometrioid adenocarcinomas: a clinicopathologic and immunohistochemical study of a group of problematic cases." Am J Surg Pathol 28(12): 1568-78.

⁶ Reid-Nicholson M, Iyengar P, Hummer AJ, et al. Immunophenotypic diversity of endometrial adenocarcinomas: implications for differential diagnosis. Mod Pathol 2006; 19:1091-100

This page last revised 13.8.2006.

©SMUHT/PW Bishop